Search for Articles:
Title / Keyword
Author / Affiliation / Email
Journal
Article Type
 
 
Advanced Search
 
Section
Special Issue
Volume
Issue
Number
Page
 
6.7
4.6
Journals
Molecules
Special Issues
Bioconjugation Strategies in Drug Delivery and Molecular Imaging
molecules-logo
Submit to Molecules Review for Molecules Propose a Special Issue

Journal Menu

► Journal Menu

Journal Browser

► Journal Browser
share announcement

Bioconjugation Strategies in Drug Delivery and Molecular Imaging

A special issue of Molecules (ISSN 1420-3049). This special issue belongs to the section "Medicinal Chemistry".

Deadline for manuscript submissions: closed (31 July 2021) | Viewed by 89665

Special Issue Editors

Dr. Andrea Trabocchi

E-Mail Website
Guest Editor
Department of Chemistry “Ugo Schiff”, University of Florence, 50019 Sesto Fiorentino, Italy
Interests: drug discovery; organic synthesis; medicinal chemistry; molecular imaging; diversity-oriented synthesis; peptidomimetics; chemoinformatics; enzyme inhibitors; angiogenesis; Alzheimer’s disease
Special Issues, Collections and Topics in MDPI journals
Dr. Elena Lenci

E-Mail Website
Guest Editor
Università degli Studi di Firenze, via della Lastruccia 13, I-50019 Sesto Fiorentino, Florence, Italy
Interests: drug discovery; carbohydrate chemistry; medicinal chemistry; chemoinformatics; enzyme inhibitors; matrix metalloproteases

Special Issue Information

Dear Colleagues,

Over the last several years, the field of bioconjugate chemistry has advanced greatly, with an increasing number of publications reporting advances on novel reactions and reagents along with their use in a variety of bioconjugation techniques and for the development of new molecular constructs. This approach has been pursued thoroughly for the conjugation of antibodies, nucleic acids, lipids, carbohydrates, or other biologically active molecules and their analogues with any molecule adding useful properties, including nanostructured materials. Specifically, the combination of monoclonal antibodies or small molecules specific to cell surface receptors with potent drugs linked via a chemical linker is being pursued as a modern and effective therapeutic approach, as demonstrated by the successful development of antibody–drug conjugates, with five approved drugs on the market.
Moreover, bioconjugation chemistry is instrumental in new approaches to targeted molecular imaging applications for the non-invasive identification, visualization, characterization, and quantification of biological processes occurring in living organisms. This important field of research with high technology content is being addressed by several approaches that have found application in clinical practice and preclinical research and aim to link a bioactive molecule with a imaging tag, including radioactive probes in PET and SPECT imaging, contrast agents in MRI, and other chemical entities for exploiting optical and ultrasound imaging.
This Special Issue of Molecules aims to collect contributions on recent trends and advances in the field of bioconjugation, specifically addressing novel chemical methodologies and reagents as well as significant applications in targeted delivery and molecular imaging in all biomedical areas. We solicit contributions on all topics connected to this area, including, but not limited to:

  • methods and reagents in bioconjugate chemistry;
  • synthesis of small-molecule–drug conjugates;
  • synthesis of antibody–drug conjugates;
  • drug delivery applications in oncology and central nervous system (CNS) diseases;
  • bioconjugate chemistry and molecular imaging applications;
  • applications of nanotechnology to drug delivery and molecular imaging.

Prof. Dr. Andrea Trabocchi
Dr. Elena Lenci
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Molecules is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2700 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • targeted delivery
  • antibody–drug conjugate
  • small molecules
  • positron emission tomography
  • magnetic resonance imaging
  • cancer research
  • precision medicine
  • nanotechnology

Published Papers (24 papers)

Download All Papers
Order results
Result details
Show export options expand_more Show export options expand_less
Select all
Export citation of selected articles as:

Research

Jump to: Review

29 pages, 5127 KiB  
Article
Molecular Engineering of E. coli Bacterioferritin: A Versatile Nanodimensional Protein Cage
by Anton M. van der Ven, Hawa Gyamfi, Uthaiwan Suttisansanee, Muhammad S. Ahmad, Zhengding Su, Robert M. Taylor, Amanda Poole, Sorina Chiorean, Elisabeth Daub, Taylor Urquhart and John F. Honek
Molecules 2023, 28(12), 4663; https://0-doi-org.brum.beds.ac.uk/10.3390/molecules28124663 - 09 Jun 2023
Viewed by 1544
Abstract
Currently, intense interest is focused on the discovery and application of new multisubunit cage proteins and spherical virus capsids to the fields of bionanotechnology, drug delivery, and diagnostic imaging as their internal cavities can serve as hosts for fluorophores or bioactive molecular cargo. [...] Read more.
Currently, intense interest is focused on the discovery and application of new multisubunit cage proteins and spherical virus capsids to the fields of bionanotechnology, drug delivery, and diagnostic imaging as their internal cavities can serve as hosts for fluorophores or bioactive molecular cargo. Bacterioferritin is unusual in the ferritin protein superfamily of iron-storage cage proteins in that it contains twelve heme cofactors and is homomeric. The goal of the present study is to expand the capabilities of ferritins by developing new approaches to molecular cargo encapsulation employing bacterioferritin. Two strategies were explored to control the encapsulation of a diverse range of molecular guests compared to random entrapment, a predominant strategy employed in this area. The first was the inclusion of histidine-tag peptide fusion sequences within the internal cavity of bacterioferritin. This approach allowed for the successful and controlled encapsulation of a fluorescent dye, a protein (fluorescently labeled streptavidin), or a 5 nm gold nanoparticle. The second strategy, termed the heme-dependent cassette strategy, involved the substitution of the native heme with heme analogs attached to (i) fluorescent dyes or (ii) nickel-nitrilotriacetate (NTA) groups (which allowed for controllable encapsulation of a histidine-tagged green fluorescent protein). An in silico docking approach identified several small molecules able to replace the heme and capable of controlling the quaternary structure of the protein. A transglutaminase-based chemoenzymatic approach to surface modification of this cage protein was also accomplished, allowing for future nanoparticle targeting. This research presents novel strategies to control a diverse set of molecular encapsulations and adds a further level of sophistication to internal protein cavity engineering. Full article
(This article belongs to the Special Issue Bioconjugation Strategies in Drug Delivery and Molecular Imaging)
►▼ Show Figures

Figure 1

9 pages, 2101 KiB  
Communication
Novel Bifunctional [16]aneS4-Derived Chelators for Soft Radiometals
by Natan J. W. Straathof, Charlotte B. Magnus, Fedor Zhuravlev and Andreas I. Jensen
Molecules 2021, 26(15), 4603; https://0-doi-org.brum.beds.ac.uk/10.3390/molecules26154603 - 29 Jul 2021
Cited by 1 | Viewed by 2218
Abstract
The field of targeted radionuclide therapy is rapidly growing, highlighting the need for wider radionuclide availability. Soft Lewis acid ions, such as radioisotopes of platinum, rhodium and palladium, are particularly underdeveloped. This is due in part to a lack of compatible bifunctional chelators. [...] Read more.
The field of targeted radionuclide therapy is rapidly growing, highlighting the need for wider radionuclide availability. Soft Lewis acid ions, such as radioisotopes of platinum, rhodium and palladium, are particularly underdeveloped. This is due in part to a lack of compatible bifunctional chelators. These allow for the practical bioconjugation to targeting vectors, in turn enabling radiolabeling. The [16]andS4 macrocycle has been reported to chelate a number of relevant soft metal ions. In this work, we present a procedure for synthesizing [16]andS4 in 45% yield (five steps, 12% overall yield), together with a selection of strategies for preparing bifunctional derivatives. An ester-linked N-hydroxysuccimide ester (NHS, seven steps, 4% overall yield), an ether-linked isothiocyanate (NCS, eight steps, 5% overall yield) and an azide derivative were prepared. In addition, a new route to a carbon-carbon linked carboxylic acid functionalized derivative is presented. Finally, a general method for conjugating the NHS and NCS derivatives to a polar peptide (octreotide) is presented, by dissolution in water:acetonitrile (1:1), buffered to pH 9.4 using borate. The reported compounds will be readily applicable in radiopharmaceutical chemistry, by facilitating the labeling of a range of molecules, including peptides, with relevant soft radiometal ions. Full article
(This article belongs to the Special Issue Bioconjugation Strategies in Drug Delivery and Molecular Imaging)
►▼ Show Figures

Graphical abstract

12 pages, 13174 KiB  
Article
Effective Tumor Targeting by EphA2-Agonist-Biotin-Streptavidin Conjugates
by Parima Udompholkul, Carlo Baggio, Luca Gambini, Yu Sun, Ming Zhao, Robert M. Hoffman and Maurizio Pellecchia
Molecules 2021, 26(12), 3687; https://0-doi-org.brum.beds.ac.uk/10.3390/molecules26123687 - 17 Jun 2021
Cited by 2 | Viewed by 2898
Abstract
We recently reported on a potent synthetic agent, 135H11, that selectively targets the receptor tyrosine kinase, EphA2. While 135H11 possesses a relatively high binding affinity for the ligand-binding domain of EphA2 (Kd~130 nM), receptor activation in the cell required the synthesis of dimeric [...] Read more.
We recently reported on a potent synthetic agent, 135H11, that selectively targets the receptor tyrosine kinase, EphA2. While 135H11 possesses a relatively high binding affinity for the ligand-binding domain of EphA2 (Kd~130 nM), receptor activation in the cell required the synthesis of dimeric versions of such agent (namely 135H12). This was expected given that the natural ephrin ligands also need to be dimerized or clustered to elicit agonistic activity in cell. In the present report we investigated whether the agonistic activity of 135H11 could be enhanced by biotin conjugation followed by complex formation with streptavidin. Therefore, we measured the agonistic EphA2 activity of 135H11-biotin (147B5) at various agent/streptavidin ratios, side by side with 135H12, and a scrambled version of 147B5 in pancreatic- and breast-cancer cell lines. The (147B5)n-streptavidin complexes (when n = 2, 3, 4, but not when n = 1) induced a strong receptor degradation effect in both cell lines compared to 135H12 or the (scrambled-147B5)4-streptavidin complex as a control, indicating that multimerization of the targeting agent resulted in an increased ability to cause receptor clustering and internalization. Subsequently, we prepared an Alexa-Fluor-streptavidin conjugate to demonstrate that (147B5)4-AF-streptavidin, but not the scrambled equivalent complex, concentrates in pancreatic and breast cancers in orthotopic nude-mouse models. Hence, we conclude that these novel targeting agents, with proper derivatization with imaging reagents or chemotherapy, can be used as diagnostics, and/or to deliver chemotherapy selectively to EphA2-expressing tumors. Full article
(This article belongs to the Special Issue Bioconjugation Strategies in Drug Delivery and Molecular Imaging)
►▼ Show Figures

Graphical abstract

16 pages, 1087 KiB  
Article
Modular Synthetic Approach to Carboranyl‒Biomolecules Conjugates
by Martin Kellert, Jan-Simon Jeshua Friedrichs, Nadine Anke Ullrich, Alexander Feinhals, Jonas Tepper, Peter Lönnecke and Evamarie Hey-Hawkins
Molecules 2021, 26(7), 2057; https://0-doi-org.brum.beds.ac.uk/10.3390/molecules26072057 - 03 Apr 2021
Cited by 6 | Viewed by 3012
Abstract
The development of novel, tumor-selective and boron-rich compounds as potential agents for use in boron neutron capture therapy (BNCT) represents a very important field in cancer treatment by radiation therapy. Here, we report the design and synthesis of two promising compounds that combine [...] Read more.
The development of novel, tumor-selective and boron-rich compounds as potential agents for use in boron neutron capture therapy (BNCT) represents a very important field in cancer treatment by radiation therapy. Here, we report the design and synthesis of two promising compounds that combine meta-carborane, a water-soluble monosaccharide and a linking unit, namely glycine or ethylenediamine, for facile coupling with various tumor-selective biomolecules bearing a free amino or carboxylic acid group. In this work, coupling experiments with two selected biomolecules, a coumarin derivative and folic acid, were included. The task of every component in this approach was carefully chosen: the carborane moiety supplies ten boron atoms, which is a tenfold increase in boron content compared to the l-boronophenylalanine (l-BPA) presently used in BNCT; the sugar moiety compensates for the hydrophobic character of the carborane; the linking unit, depending on the chosen biomolecule, acts as the connection between the tumor-selective component and the boron-rich moiety; and the respective tumor-selective biomolecule provides the necessary selectivity. This approach makes it possible to develop a modular and feasible strategy for the synthesis of readily obtainable boron-rich agents with optimized properties for potential applications in BNCT. Full article
(This article belongs to the Special Issue Bioconjugation Strategies in Drug Delivery and Molecular Imaging)
►▼ Show Figures

Graphical abstract

25 pages, 4104 KiB  
Article
Synthesis and Biological Evaluation of 99mTc(I) Tricarbonyl Complexes Dual-Targeted at Tumoral Mitochondria
by Diogo Figueiredo, Célia Fernandes, Francisco Silva, Elisa Palma, Paula Raposinho, Ana Belchior, Pedro Vaz and António Paulo
Molecules 2021, 26(2), 441; https://0-doi-org.brum.beds.ac.uk/10.3390/molecules26020441 - 15 Jan 2021
Cited by 9 | Viewed by 2990
Abstract
For effective Auger therapy of cancer, the Auger-electron emitters must be delivered to the tumor cells in close proximity to a radiosensitive cellular target. Nuclear DNA is considered the most relevant target of Auger electrons to have augmented radiotoxic effects and significant cell [...] Read more.
For effective Auger therapy of cancer, the Auger-electron emitters must be delivered to the tumor cells in close proximity to a radiosensitive cellular target. Nuclear DNA is considered the most relevant target of Auger electrons to have augmented radiotoxic effects and significant cell death. However, there is a growing body of evidence that other targets, such as the mitochondria, could be relevant subcellular targets in Auger therapy. Thus, we developed dual-targeted 99mTc(I) tricarbonyl complexes containing a triphenylphosphonium (TPP) moiety to promote accumulation of 99mTc in the mitochondria, and a bombesin peptide to provide specificity towards the gastrin releasing peptide receptor (GRPr) overexpressed in prostate cancer cells. The designed dual-targeted complex, 99mTc-TPP-BBN, is efficiently internalized by human prostate cancer PC3 cells through a specific GRPr-mediated mechanism of uptake. Moreover, the radioconjugate provided an augmented accumulation of 99mTc in the mitochondria of the target tumor cells, most probably following its intracellular cleavage by cathepsin B. In addition, 99mTc-TPP-BBN showed an enhanced ability to reduce the survival of PC3 cells, in a dose-dependent manner. Full article
(This article belongs to the Special Issue Bioconjugation Strategies in Drug Delivery and Molecular Imaging)
►▼ Show Figures

Figure 1

8 pages, 2030 KiB  
Article
Micelle-in-Liposomes for Sustained Delivery of Anticancer Agents That Promote Potent TRAIL-Induced Cancer Cell Apoptosis
by Zhenjiang Zhang, Sagar B. Patel and Michael R. King
Molecules 2021, 26(1), 157; https://0-doi-org.brum.beds.ac.uk/10.3390/molecules26010157 - 31 Dec 2020
Cited by 11 | Viewed by 2852
Abstract
Tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) induces cancer cell-specific apoptosis and has garnered intense interest as a promising agent for cancer treatment. However, the development of TRAIL has been hampered in part because most human cancer cells are resistant to TRAIL. A [...] Read more.
Tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) induces cancer cell-specific apoptosis and has garnered intense interest as a promising agent for cancer treatment. However, the development of TRAIL has been hampered in part because most human cancer cells are resistant to TRAIL. A few small molecules including natural compounds such as piperlongumine (PL) have been reported to sensitize cancer cells to TRAIL. We prepared a novel type of nanomaterial, micelle-in-liposomes (MILs) for solubilization and delivery of PL. PL-loaded MILs were used to sensitize cancer cells to TRAIL. As visualized by cryo-TEM, micelles were successfully loaded inside the aqueous core of liposomes. The MILs increased the water solubility of PL by ~20 fold. A sustained PL release from MILs in physiologically relevant buffer over 7 days was achieved, indicating that the liposomes prevented premature drug release from the micelles in the MILs. Also demonstrated is a potent synergistic apoptotic effect in cancer cells by PL MILs in conjunction with liposomal TRAIL. MILs provide a new formulation and delivery vehicle for hydrophobic anticancer agents, which can be used alone or in combination with TRAIL to promote cancer cell death. Full article
(This article belongs to the Special Issue Bioconjugation Strategies in Drug Delivery and Molecular Imaging)
►▼ Show Figures

Figure 1

21 pages, 3131 KiB  
Article
Polypeptide-Based Molecular Platform and Its Docetaxel/Sulfo-Cy5-Containing Conjugate for Targeted Delivery to Prostate Specific Membrane Antigen
by Stanislav A. Petrov, Aleksei E. Machulkin, Anastasia A. Uspenskaya, Nikolay Y. Zyk, Ekaterina A. Nimenko, Anastasia S. Garanina, Rostislav A. Petrov, Vladimir I. Polshakov, Yuri K. Grishin, Vitaly A. Roznyatovsky, Nikolay V. Zyk, Alexander G. Majouga and Elena K. Beloglazkina
Molecules 2020, 25(24), 5784; https://0-doi-org.brum.beds.ac.uk/10.3390/molecules25245784 - 08 Dec 2020
Cited by 13 | Viewed by 2884
Abstract
A strategy for stereoselective synthesis of molecular platform for targeted delivery of bimodal therapeutic or theranostic agents to the prostate-specific membrane antigen (PSMA) receptor was developed. The proposed platform contains a urea-based, PSMA-targeting Glu-Urea-Lys (EuK) fragment as a vector moiety and tripeptide linker [...] Read more.
A strategy for stereoselective synthesis of molecular platform for targeted delivery of bimodal therapeutic or theranostic agents to the prostate-specific membrane antigen (PSMA) receptor was developed. The proposed platform contains a urea-based, PSMA-targeting Glu-Urea-Lys (EuK) fragment as a vector moiety and tripeptide linker with terminal amide and azide groups for subsequent addition of two different therapeutic and diagnostic agents. The optimal method for this molecular platform synthesis includes (a) solid-phase assembly of the polypeptide linker, (b) coupling of this linker with the vector fragment, (c) attachment of 3-aminopropylazide, and (d) amide and carboxylic groups deprotection. A bimodal theranostic conjugate of the proposed platform with a cytostatic drug (docetaxel) and a fluorescent label (Sulfo-Cy5) was synthesized to demonstrate its possible sequential conjugation with different functional molecules. Full article
(This article belongs to the Special Issue Bioconjugation Strategies in Drug Delivery and Molecular Imaging)
►▼ Show Figures

Graphical abstract

20 pages, 2693 KiB  
Article
In Silico Analysis and In Vitro Characterization of the Bioactive Profile of Three Novel Peptides Identified from 19 kDa α-Zein Sequences of Maize
by Jorge L. Díaz-Gómez, Ines Neundorf, Laura-Margarita López-Castillo, Fabiola Castorena-Torres, Sergio O. Serna-Saldívar and Silverio García-Lara
Molecules 2020, 25(22), 5405; https://0-doi-org.brum.beds.ac.uk/10.3390/molecules25225405 - 19 Nov 2020
Cited by 13 | Viewed by 2901
Abstract
In this study, we characterized three novel peptides derived from the 19 kDa α-zein, and determined their bioactive profile in vitro and developed a structural model in silico. The peptides, 19ZP1, 19ZP2 and 19ZP3, formed α-helical structures and had positive and negative electrostatic [...] Read more.
In this study, we characterized three novel peptides derived from the 19 kDa α-zein, and determined their bioactive profile in vitro and developed a structural model in silico. The peptides, 19ZP1, 19ZP2 and 19ZP3, formed α-helical structures and had positive and negative electrostatic potential surfaces (range of −1 to +1). According to the in silico algorithms, the peptides displayed low probabilities for cytotoxicity (≤0.05%), cell penetration (10–33%) and antioxidant activities (9–12.5%). Instead, they displayed a 40% probability for angiotensin-converting enzyme (ACE) inhibitory activity. For in vitro characterization, peptides were synthesized by solid phase synthesis and tested accordingly. We assumed α-helical structures for 19ZP1 and 19ZP2 under hydrophobic conditions. The peptides displayed antioxidant activity and ACE-inhibitory activity, with 19ZP1 being the most active. Our results highlight that the 19 kDa α-zein sequences could be explored as a source of bioactive peptides, and indicate that in silico approaches are useful to predict peptide bioactivities, but more structural analysis is necessary to obtain more accurate data. Full article
(This article belongs to the Special Issue Bioconjugation Strategies in Drug Delivery and Molecular Imaging)
►▼ Show Figures

Graphical abstract

20 pages, 3005 KiB  
Article
Cathepsin B-Cleavable Cyclopeptidic Chemotherapeutic Prodrugs
by Viktorija Herceg, Jordan Bouilloux, Karolina Janikowska, Eric Allémann and Norbert Lange
Molecules 2020, 25(18), 4285; https://0-doi-org.brum.beds.ac.uk/10.3390/molecules25184285 - 18 Sep 2020
Cited by 8 | Viewed by 3037
Abstract
Cyclopeptidic chemotherapeutic prodrugs (cPCPs) are macromolecular protease-sensitive doxorubicin (DOX) prodrugs synthesized from a cyclodecapeptidic scaffold, termed Regioselectively Addressable Functionalized Template (RAFT). In order to increase the chemotherapeutic potential of DOX and limit its toxicity, we used a Cathepsin B (Cat B)-sensitive prodrug concept [...] Read more.
Cyclopeptidic chemotherapeutic prodrugs (cPCPs) are macromolecular protease-sensitive doxorubicin (DOX) prodrugs synthesized from a cyclodecapeptidic scaffold, termed Regioselectively Addressable Functionalized Template (RAFT). In order to increase the chemotherapeutic potential of DOX and limit its toxicity, we used a Cathepsin B (Cat B)-sensitive prodrug concept for its targeted release since this enzyme is frequently overexpressed in cancer cells. Copper-free “click” chemistry was used to synthesize cPCPs containing up to four DOX moieties tethered to the upper face of the scaffold through a Cat B-cleavable peptidic linker (GAGRRAAG). On the lower part, PEG 5, 10 and 20 kDa and a fifth peptidyl DOX moiety were grafted in order to improve the solubility, bioavailability and pharmacokinetic profiles of the compound. In vitro results on HT1080 human fibrosarcoma cells showed that cPCPs display a delayed action that consists of a cell cycle arrest in the G2 phase comparable to DOX alone, and increased cell membrane permeability. Full article
(This article belongs to the Special Issue Bioconjugation Strategies in Drug Delivery and Molecular Imaging)
►▼ Show Figures

Graphical abstract

27 pages, 4676 KiB  
Article
Transport Oligonucleotides—A Novel System for Intracellular Delivery of Antisense Therapeutics
by Oleg V. Markov, Anton V. Filatov, Maxim S. Kupryushkin, Ivan V. Chernikov, Olga A. Patutina, Anton A. Strunov, Elena L. Chernolovskaya, Valentin V. Vlassov, Dmitrii V. Pyshnyi and Marina A. Zenkova
Molecules 2020, 25(16), 3663; https://0-doi-org.brum.beds.ac.uk/10.3390/molecules25163663 - 11 Aug 2020
Cited by 13 | Viewed by 3548
Abstract
Biological activity of antisense oligonucleotides (asON), especially those with a neutral backbone, is often attenuated by poor cellular accumulation. In the present proof-of-concept study, we propose a novel delivery system for asONs which implies the delivery of modified antisense oligonucleotides by so-called transport [...] Read more.
Biological activity of antisense oligonucleotides (asON), especially those with a neutral backbone, is often attenuated by poor cellular accumulation. In the present proof-of-concept study, we propose a novel delivery system for asONs which implies the delivery of modified antisense oligonucleotides by so-called transport oligonucleotides (tON), which are oligodeoxyribonucleotides complementary to asON conjugated with hydrophobic dodecyl moieties. Two types of tONs, bearing at the 5′-end up to three dodecyl residues attached through non-nucleotide inserts (TD series) or anchored directly to internucleotidic phosphate (TP series), were synthesized. tONs with three dodecyl residues efficiently delivered asON to cells without any signs of cytotoxicity and provided a transfection efficacy comparable to that achieved using Lipofectamine 2000. We found that, in the case of tON with three dodecyl residues, some tON/asON duplexes were excreted from the cells within extracellular vesicles at late stages of transfection. We confirmed the high efficacy of the novel and demonstrated that MDR1 mRNA targeted asON delivered by tON with three dodecyl residues significantly reduced the level of P-glycoprotein and increased the sensitivity of KB-8-5 human carcinoma cells to vinblastine. The obtained results demonstrate the efficacy of lipophilic oligonucleotide carriers and shows they are potentially capable of intracellular delivery of any kind of antisense oligonucleotides. Full article
(This article belongs to the Special Issue Bioconjugation Strategies in Drug Delivery and Molecular Imaging)
►▼ Show Figures

Figure 1

14 pages, 3929 KiB  
Article
Anti-VCAM-1 and Anti-IL4Rα Aptamer-Conjugated Super Paramagnetic Iron Oxide Nanoparticles for Enhanced Breast Cancer Diagnosis and Therapy
by Raja Chinnappan, Achraf Al Faraj, Anas M. Abdel Rahman, Khalid M. Abu-Salah, Fouzi Mouffouk and Mohammed Zourob
Molecules 2020, 25(15), 3437; https://0-doi-org.brum.beds.ac.uk/10.3390/molecules25153437 - 29 Jul 2020
Cited by 18 | Viewed by 3176
Abstract
The surface protein overexpressed on cancer cells can be used as biomarkers for early detection of specific diseases. Anti-VCAM-1 and anti-IL4Rα DNA aptamers specific to VCAM-1 and IL4Rα receptors that are overexpressed in 4T1 tumor-bearing mice could be used as potential biomarker for [...] Read more.
The surface protein overexpressed on cancer cells can be used as biomarkers for early detection of specific diseases. Anti-VCAM-1 and anti-IL4Rα DNA aptamers specific to VCAM-1 and IL4Rα receptors that are overexpressed in 4T1 tumor-bearing mice could be used as potential biomarker for both diagnostic and therapeutic applications in cancer biology. Cell Viability and luciferase assay of 4T1-Luc2 cancer cells in the presence of anti-VCAM-1 ssDNA or anti-IL4Rα RNA aptamers was assessed by monitoring the changes in the absorbance and the fluorescence of Alamar blue dye. The aptamer-conjugated SPIO magnetic beads, used for the selective targeting to tumor sites, were monitored using noninvasive MRI and Bioluminescence imaging (BLI). Cell viability and luciferase assays showed that both anti-VCAM-1 and anti-IL4Rα aptamers favor the depletion of cancer cells and limit tumor progression. Microscopic analyses confirmed that the target specific aptamers significantly trigger tumor cell apoptosis and limit cancer cell growth in vitro. The intravenous injection of SPIO nanoparticle-conjugated aptamers were further confirmed using noninvasive MRI and Bioluminescence imaging. Anti-VCAM1 and anti-IL4Rα aptamers, specific to VCAM-1 and IL4Rα receptors overexpressed in 4T1-Luc2 tumor-bearing mice, were used as diagnostic and therapeutic tools. Full article
(This article belongs to the Special Issue Bioconjugation Strategies in Drug Delivery and Molecular Imaging)
►▼ Show Figures

Figure 1

10 pages, 1293 KiB  
Communication
Synthesis and Immunological Evaluation of a Single Molecular Construct MUC1 Vaccine Containing l-Rhamnose Repeating Units
by Md Kamal Hossain, Abhishek Vartak, Steven J. Sucheck and Katherine A. Wall
Molecules 2020, 25(14), 3137; https://0-doi-org.brum.beds.ac.uk/10.3390/molecules25143137 - 09 Jul 2020
Cited by 4 | Viewed by 2866
Abstract
A rhamnose targeting strategy for generating effective anticancer vaccines was successful in our previous studies. We showed that by utilizing natural anti-rhamnose antibodies, a rhamnose-containing vaccine can be targeted to antigen-presenting cells, such as dendritic cells. In this case, rhamnose (Rha) was linked [...] Read more.
A rhamnose targeting strategy for generating effective anticancer vaccines was successful in our previous studies. We showed that by utilizing natural anti-rhamnose antibodies, a rhamnose-containing vaccine can be targeted to antigen-presenting cells, such as dendritic cells. In this case, rhamnose (Rha) was linked directly to the liposomes bearing the antigen. However, in the current approach, we conjugated a multivalent Tri-Rha ligand with the antigen itself, making it a single component vaccine construct, unlike the previous two-component vaccine construct where Rha cholesterol and Mucin1 (MUC1) antigen were both linked separately to the liposomes. Synthesis required the development of a linker for coupling of the Rha-Ser residues. We compared those two systems in a mouse model and found increased production of anti-MUC1 antibodies and more primed antigen-specific CD4+ T cells in both of the targeted approaches when compared to the control group, suggesting that this one-component vaccine construct could be a potential design used in our MUC1 targeting mechanisms. Full article
(This article belongs to the Special Issue Bioconjugation Strategies in Drug Delivery and Molecular Imaging)
►▼ Show Figures

Figure 1

16 pages, 3553 KiB  
Article
Albumin-Binding PSMA Radioligands: Impact of Minimal Structural Changes on the Tissue Distribution Profile
by Luisa M. Deberle, Viviane J. Tschan, Francesca Borgna, Fan Sozzi-Guo, Peter Bernhardt, Roger Schibli and Cristina Müller
Molecules 2020, 25(11), 2542; https://0-doi-org.brum.beds.ac.uk/10.3390/molecules25112542 - 29 May 2020
Cited by 12 | Viewed by 3395
Abstract
The concept of using ibuprofen as an albumin-binding entity was recently demonstrated by the development of [177Lu]Lu-Ibu-PSMA-01. In the present study, we designed a novel ibuprofen-containing radioligand (Ibu-PSMA-02) with subtle structural changes regarding the linker entity in order to investigate a [...] Read more.
The concept of using ibuprofen as an albumin-binding entity was recently demonstrated by the development of [177Lu]Lu-Ibu-PSMA-01. In the present study, we designed a novel ibuprofen-containing radioligand (Ibu-PSMA-02) with subtle structural changes regarding the linker entity in order to investigate a potential impact on the in vitro and in vivo properties. Ibu-PSMA-02 was prepared using solid-phase synthesis techniques and labeled with lutetium-177. [177Lu]Lu-Ibu-PSMA-02 was evaluated in vitro with regard to its plasma protein-binding properties, PSMA affinity and uptake into PSMA-expressing PC-3 PIP tumor cells. The tissue distribution profile of [177Lu]Lu-Ibu-PSMA-02 was assessed in tumor-bearing mice and dose estimations were performed. The in vitro characteristics of [177Lu]Lu-Ibu-PSMA-02 were similar to those previously obtained for [177Lu]Lu-Ibu-PSMA-01 with respect to plasma protein-binding, PSMA affinity and tumor cell uptake. The in vivo studies revealed, however, an unprecedentedly high uptake of [177Lu]Lu-Ibu-PSMA-02 in PC-3 PIP tumors, resulting in an increased absorbed tumor dose of 7.7 Gy/MBq as compared to 5.1 Gy/MBq calculated for [177Lu]Lu-Ibu-PSMA-01. As a consequence of the high tumor accumulation, [177Lu]Lu-Ibu-PSMA-02 showed higher tumor-to-background ratios than [177Lu]Lu-Ibu-PSMA-01. This study exemplified that smallest structural changes in the linker entity of PSMA radioligands may have a significant impact on their pharmacokinetic profiles and, thus, may be applied as a means for ligand design optimization. Full article
(This article belongs to the Special Issue Bioconjugation Strategies in Drug Delivery and Molecular Imaging)
►▼ Show Figures

Figure 1

23 pages, 3909 KiB  
Article
Dual miRNases for Triple Incision of miRNA Target: Design Concept and Catalytic Performance
by Olga Patutina, Daria Chiglintseva, Elena Bichenkova, Svetlana Gaponova, Nadezhda Mironova, Valentin Vlassov and Marina Zenkova
Molecules 2020, 25(10), 2459; https://0-doi-org.brum.beds.ac.uk/10.3390/molecules25102459 - 25 May 2020
Cited by 8 | Viewed by 2704
Abstract
Irreversible destruction of disease-associated regulatory RNA sequences offers exciting opportunities for safe and powerful therapeutic interventions against human pathophysiology. In 2017, for the first time we introduced miRNAses–miRNA-targeted conjugates of a catalytic peptide and oligonucleotide capable of cleaving an miRNA target. Herein, we [...] Read more.
Irreversible destruction of disease-associated regulatory RNA sequences offers exciting opportunities for safe and powerful therapeutic interventions against human pathophysiology. In 2017, for the first time we introduced miRNAses–miRNA-targeted conjugates of a catalytic peptide and oligonucleotide capable of cleaving an miRNA target. Herein, we report the development of Dual miRNases against oncogenic miR-21, miR-155, miR-17 and miR-18a, each containing the catalytic peptide placed in-between two short miRNA-targeted oligodeoxyribonucleotide recognition motifs. Substitution of adenines with 2-aminoadenines in the sequence of oligonucleotide “shoulders” of the Dual miRNase significantly enhanced the efficiency of hybridization with the miRNA target. It was shown that sequence-specific cleavage of the target by miRNase proceeded metal-independently at pH optimum 5.5–7.5 with an efficiency varying from 15% to 85%, depending on the miRNA sequence. A distinct advantage of the engineered nucleases is their ability to additionally recruit RNase H and cut miRNA at three different locations. Such cleavage proceeds at the central part by Dual miRNase, and at the 5′- and 3′-regions by RNase H, which significantly increases the efficiency of miRNA degradation. Due to increased activity at lowered pH Dual miRNases could provide an additional advantage in acidic tumor conditions and may be considered as efficient tumor-selective RNA-targeted therapeutic. Full article
(This article belongs to the Special Issue Bioconjugation Strategies in Drug Delivery and Molecular Imaging)
►▼ Show Figures

Figure 1

24 pages, 5234 KiB  
Article
Carbonic Anhydrase-IX Guided Albumin Nanoparticles for Hypoxia-mediated Triple-Negative Breast Cancer Cell Killing and Imaging of Patient-derived Tumor
by Katyayani Tatiparti, Mohd Ahmar Rauf, Samaresh Sau and Arun K. Iyer
Molecules 2020, 25(10), 2362; https://0-doi-org.brum.beds.ac.uk/10.3390/molecules25102362 - 19 May 2020
Cited by 16 | Viewed by 3741
Abstract
Triple-Negative Breast Cancer (TNBC) is considered as the most onerous cancer subtype, lacking the estrogen, progesterone, and HER2 receptors. Evaluating new markers is an unmet need for improving targeted therapy against TNBC. TNBC depends on several factors, including hypoxia development, which contributes to [...] Read more.
Triple-Negative Breast Cancer (TNBC) is considered as the most onerous cancer subtype, lacking the estrogen, progesterone, and HER2 receptors. Evaluating new markers is an unmet need for improving targeted therapy against TNBC. TNBC depends on several factors, including hypoxia development, which contributes to therapy resistance, immune evasion, and tumor stroma formation. In this study, we studied the curcumin analogue (3,4-Difluorobenzylidene Curcumin; CDF) encapsulated bovine serum albumin (BSA) nanoparticle for tumor targeting. For tumor targeting, we conjugated Acetazolamide (ATZ) with CDF and encapsulated it in the BSA to form a nanoparticle (namely BSA-CDF-ATZ). The in vitro cytotoxicity study suggested that BSA-CDF-ATZ is more efficient when compared to free CDF. The BSA-CDF-ATZ nanoparticles showed significantly higher cell killing in hypoxic conditions compared to normoxic conditions, suggesting better internalization of the nanoparticles into cancer cells under hypoxia. Fluorescent-dye labeled BSA-CDF-ATZ revealed higher cell uptake of the nanoparticle compared to free dye indicative of better delivery, substantiated by a high rate of apoptosis-mediated cell death compared to free CDF. The significantly higher tumor accumulation and low liver and spleen uptake in TNBC patient-derived tumor xenograft models confirm the significant potential of BSA-CDF-ATZ for targeted TNBC imaging and therapy. Full article
(This article belongs to the Special Issue Bioconjugation Strategies in Drug Delivery and Molecular Imaging)
►▼ Show Figures

Graphical abstract

11 pages, 847 KiB  
Article
Trimeric Small Interfering RNAs and Their Cholesterol-Containing Conjugates Exhibit Improved Accumulation in Tumors, but Dramatically Reduced Silencing Activity
by Ivan V. Chernikov, Daniil V. Gladkikh, Ulyana A. Karelina, Mariya I. Meschaninova, Alya G. Ven’yaminova, Valentin V. Vlassov and Elena L. Chernolovskaya
Molecules 2020, 25(8), 1877; https://0-doi-org.brum.beds.ac.uk/10.3390/molecules25081877 - 18 Apr 2020
Cited by 6 | Viewed by 2937
Abstract
Cholesterol derivatives of nuclease-resistant, anti-MDR1 small-interfering RNAs were designed to contain a 2’-OMe-modified 21-bp siRNA and a 63-bp TsiRNA in order to investigate their accumulation and silencing activity in vitro and in vivo. The results showed that increasing the length of the [...] Read more.
Cholesterol derivatives of nuclease-resistant, anti-MDR1 small-interfering RNAs were designed to contain a 2’-OMe-modified 21-bp siRNA and a 63-bp TsiRNA in order to investigate their accumulation and silencing activity in vitro and in vivo. The results showed that increasing the length of the RNA duplex in such a conjugate increases its biological activity when delivered using a transfection agent. However, the efficiency of accumulation in human drug-resistant KB-8-5 cells during delivery in vitro in a carrier-free mode was reduced as well as efficiency of target gene silencing. TsiRNAs demonstrated a similar biodistribution in KB-8-5 xenograft tumor-bearing SCID mice with more efficient accumulation in organs and tumors than cholesterol-conjugated canonical siRNAs; however, this accumulation did not provide a silencing effect. The lack of correlation between the accumulation in the organ and the silencing activity of cholesterol conjugates of siRNAs of different lengths can be attributed to the fact that trimeric Ch-TsiRNA lags mainly in the intercellular space and does not penetrate sufficiently into the cytoplasm of the cell. Increased accumulation in the organs and in the tumor, by itself, shows that using siRNA with increased molecular weight is an effective approach to control biodistribution and delivery to the target organ. Full article
(This article belongs to the Special Issue Bioconjugation Strategies in Drug Delivery and Molecular Imaging)
►▼ Show Figures

Figure 1

14 pages, 2502 KiB  
Article
A New Class of Smart Gadolinium Contrast Agent for Tissue pH Probing Using Magnetic Resonance Imaging
by Fouzi Mouffouk, Hacene Serrai, Sourav Bhaduri, Rik Achten, Mozhdeh Seyyedhamzeh, Ali A. Husain, Abdullah Alhendal and Mohammed Zourob
Molecules 2020, 25(7), 1513; https://0-doi-org.brum.beds.ac.uk/10.3390/molecules25071513 - 26 Mar 2020
Cited by 4 | Viewed by 3573
Abstract
Detecting tissue pH in vivo is extremely vital for medical diagnosis and formulation of treatment decisions. To this end, many investigations have been carried out to develop an accurate and efficient method of in vivo pH measurement. Most of the techniques developed so [...] Read more.
Detecting tissue pH in vivo is extremely vital for medical diagnosis and formulation of treatment decisions. To this end, many investigations have been carried out to develop an accurate and efficient method of in vivo pH measurement. Most of the techniques developed so far suffer from inadequate accuracy, due to poor sensitivity at low concentration of the target or nonspecific interactions within the tissue matrix. To overcome these issues, we describe herein the development of a simple, yet reliable, way to estimate pH with high precision using a Gd(III)-DOTA-silyl-based acid-labile group as a pH-sensitive contrast agent with Magnetic Resonance Imaging (MRI). With this method, a change in T 1 weighted image intensity of the newly developed pH-sensitive contrast is directly linked to the proton concentration in the media. As a result, we were able estimate the pH of the target with 95% reliability. Full article
(This article belongs to the Special Issue Bioconjugation Strategies in Drug Delivery and Molecular Imaging)
►▼ Show Figures

Figure 1

Review

Jump to: Research

41 pages, 28233 KiB  
Review
Enzymatic Methods for the Site-Specific Radiolabeling of Targeting Proteins
by Cristina Bolzati and Barbara Spolaore
Molecules 2021, 26(12), 3492; https://0-doi-org.brum.beds.ac.uk/10.3390/molecules26123492 - 08 Jun 2021
Cited by 13 | Viewed by 3825
Abstract
Site-specific conjugation of proteins is currently required to produce homogenous derivatives for medicine applications. Proteins derivatized at specific positions of the polypeptide chain can actually show higher stability, superior pharmacokinetics, and activity in vivo, as compared with conjugates modified at heterogeneous sites. Moreover, [...] Read more.
Site-specific conjugation of proteins is currently required to produce homogenous derivatives for medicine applications. Proteins derivatized at specific positions of the polypeptide chain can actually show higher stability, superior pharmacokinetics, and activity in vivo, as compared with conjugates modified at heterogeneous sites. Moreover, they can be better characterized regarding the composition of the derivatization sites as well as the conformational and activity properties. To this aim, several site-specific derivatization approaches have been developed. Among these, enzymes are powerful tools that efficiently allow the generation of homogenous protein–drug conjugates under physiological conditions, thus preserving their native structure and activity. This review will summarize the progress made over the last decade on the use of enzymatic-based methodologies for the production of site-specific labeled immunoconjugates of interest for nuclear medicine. Enzymes used in this field, including microbial transglutaminase, sortase, galactosyltransferase, and lipoic acid ligase, will be overviewed and their recent applications in the radiopharmaceutical field will be described. Since nuclear medicine can benefit greatly from the production of homogenous derivatives, we hope that this review will aid the use of enzymes for the development of better radio-conjugates for diagnostic and therapeutic purposes. Full article
(This article belongs to the Special Issue Bioconjugation Strategies in Drug Delivery and Molecular Imaging)
►▼ Show Figures

Figure 1

24 pages, 2420 KiB  
Review
Recent Advances and Trends in Chemical CPP–Drug Conjugation Techniques
by Félix Gayraud, Merlin Klußmann and Ines Neundorf
Molecules 2021, 26(6), 1591; https://0-doi-org.brum.beds.ac.uk/10.3390/molecules26061591 - 13 Mar 2021
Cited by 12 | Viewed by 3968
Abstract
This review summarizes recent developments in conjugation techniques for the synthesis of cell-penetrating peptide (CPP)–drug conjugates targeting cancer cells. We will focus on small organic molecules as well as metal complexes that were used as cytostatic payloads. Moreover, two principle ways of coupling [...] Read more.
This review summarizes recent developments in conjugation techniques for the synthesis of cell-penetrating peptide (CPP)–drug conjugates targeting cancer cells. We will focus on small organic molecules as well as metal complexes that were used as cytostatic payloads. Moreover, two principle ways of coupling chemistry will be discussed direct conjugation as well as the use of bifunctional linkers. While direct conjugation of the drug to the CPP is still popular, the use of bifunctional linkers seems to gain increasing attention as it offers more advantages related to the linker chemistry. Thus, three main categories of linkers will be highlighted, forming either disulfide acid-sensitive or stimuli-sensitive bonds. All techniques will be thoroughly discussed by their pros and cons with the aim to help the reader in the choice of the optimal conjugation technique that might be used for the synthesis of a given CPP–drug conjugate Full article
(This article belongs to the Special Issue Bioconjugation Strategies in Drug Delivery and Molecular Imaging)
►▼ Show Figures

Figure 1

18 pages, 1550 KiB  
Review
Lipid Formulations and Bioconjugation Strategies for Indomethacin Therapeutic Advances
by Anna Gliszczyńska and Marta Nowaczyk
Molecules 2021, 26(6), 1576; https://0-doi-org.brum.beds.ac.uk/10.3390/molecules26061576 - 12 Mar 2021
Cited by 12 | Viewed by 4850
Abstract
Indomethacin (IND) is a drug which after successful clinical trials became available for general prescription in 1965 and from that time is one of the most widely used anti-inflammatory drug with the highest potencies in the in vitro and in vivo models. However, [...] Read more.
Indomethacin (IND) is a drug which after successful clinical trials became available for general prescription in 1965 and from that time is one of the most widely used anti-inflammatory drug with the highest potencies in the in vitro and in vivo models. However, despite its high therapeutic efficacy in relieving the symptoms of certain arthritis and in treating gout or collagen diseases, administration of IND causes a number of adverse effects, such as gastrointestinal ulceration, frequent central nervous system disorders and renal toxicity. These obstacles significantly limit the practical applications of IND and make that 10–20% of patients discontinue its use. Therefore, during the last three decades many attempts have been made to design novel formulations of IND aimed to increase its therapeutic benefits minimizing its adverse effects. In this review we summarize pharmacological information about IND and analyze its new lipid formulations and lipid bioconjugates as well as discuss their efficacy and potential application. Full article
(This article belongs to the Special Issue Bioconjugation Strategies in Drug Delivery and Molecular Imaging)
►▼ Show Figures

Figure 1

12 pages, 749 KiB  
Review
Co-Opting Host Receptors for Targeted Delivery of Bioconjugates—From Drugs to Bugs
by Kristen M. Tummillo and Karsten R.O. Hazlett
Molecules 2021, 26(5), 1479; https://0-doi-org.brum.beds.ac.uk/10.3390/molecules26051479 - 09 Mar 2021
Viewed by 2293
Abstract
Bioconjugation has allowed scientists to combine multiple functional elements into one biological or biochemical unit. This assembly can result in the production of constructs that are targeted to a specific site or cell type in order to enhance the response to, or activity [...] Read more.
Bioconjugation has allowed scientists to combine multiple functional elements into one biological or biochemical unit. This assembly can result in the production of constructs that are targeted to a specific site or cell type in order to enhance the response to, or activity of, the conjugated moiety. In the case of cancer treatments, selectively targeting chemotherapies to the cells of interest limit harmful side effects and enhance efficacy. Targeting through conjugation is also advantageous in delivering treatments to difficult-to-reach tissues, such as the brain or infections deep in the lung. Bacterial infections can be more selectively treated by conjugating antibiotics to microbe-specific entities; helping to avoid antibiotic resistance across commensal bacterial species. In the case of vaccine development, conjugation is used to enhance efficacy without compromising safety. In this work, we will review the previously mentioned areas in which bioconjugation has created new possibilities and advanced treatments. Full article
(This article belongs to the Special Issue Bioconjugation Strategies in Drug Delivery and Molecular Imaging)
►▼ Show Figures

Figure 1

28 pages, 3980 KiB  
Review
Recent Progress in Bioconjugation Strategies for Liposome-Mediated Drug Delivery
by Bethany Almeida, Okhil K. Nag, Katherine E. Rogers and James B. Delehanty
Molecules 2020, 25(23), 5672; https://0-doi-org.brum.beds.ac.uk/10.3390/molecules25235672 - 01 Dec 2020
Cited by 125 | Viewed by 12906
Abstract
In nanoparticle (NP)-mediated drug delivery, liposomes are the most widely used drug carrier, and the only NP system currently approved by the FDA for clinical use, owing to their advantageous physicochemical properties and excellent biocompatibility. Recent advances in liposome technology have been focused [...] Read more.
In nanoparticle (NP)-mediated drug delivery, liposomes are the most widely used drug carrier, and the only NP system currently approved by the FDA for clinical use, owing to their advantageous physicochemical properties and excellent biocompatibility. Recent advances in liposome technology have been focused on bioconjugation strategies to improve drug loading, targeting, and overall efficacy. In this review, we highlight recent literature reports (covering the last five years) focused on bioconjugation strategies for the enhancement of liposome-mediated drug delivery. These advances encompass the improvement of drug loading/incorporation and the specific targeting of liposomes to the site of interest/drug action. We conclude with a section highlighting the role of bioconjugation strategies in liposome systems currently being evaluated for clinical use and a forward-looking discussion of the field of liposomal drug delivery. Full article
(This article belongs to the Special Issue Bioconjugation Strategies in Drug Delivery and Molecular Imaging)
►▼ Show Figures

Figure 1

27 pages, 2300 KiB  
Review
Current Targets and Bioconjugation Strategies in Photodynamic Diagnosis and Therapy of Cancer
by Salvador Gomez, Allan Tsung and Zhiwei Hu
Molecules 2020, 25(21), 4964; https://0-doi-org.brum.beds.ac.uk/10.3390/molecules25214964 - 27 Oct 2020
Cited by 18 | Viewed by 3647
Abstract
Photodynamic diagnosis (PDD) and therapy (PDT) are emerging, non/minimally invasive techniques for cancer diagnosis and treatment. Both techniques require a photosensitizer and light to visualize or destroy cancer cells. However, a limitation of conventional, non-targeted PDT is poor selectivity, causing side effects. The [...] Read more.
Photodynamic diagnosis (PDD) and therapy (PDT) are emerging, non/minimally invasive techniques for cancer diagnosis and treatment. Both techniques require a photosensitizer and light to visualize or destroy cancer cells. However, a limitation of conventional, non-targeted PDT is poor selectivity, causing side effects. The bioconjugation of a photosensitizer to a tumor-targeting molecule, such as an antibody or a ligand peptide, is a way to improve selectivity. The bioconjugation strategy can generate a tumor-targeting photosensitizer conjugate specific for cancer cells, or ideally, for multiple tumor compartments to improve selectivity and efficacy, such as cancer stem cells and tumor neovasculature within the tumor microenvironment. If successful, such targeted photosensitizer conjugates can also be used for specific visualization and detection of cancer cells and/or tumor angiogenesis (an early event in tumorigenesis) with the hope of an early diagnosis of cancer. The purpose of this review is to summarize some current promising target molecules, e.g., tissue factor (also known as CD142), and the currently used bioconjugation strategies in PDT and PDD, with a focus on newly developed protein photosensitizers. These are genetically engineered photosensitizers, with the possibility of generating a fusion protein photosensitizer by recombinant DNA technology for both PDT and PDD without the need of chemical conjugation. We believe that providing an overview of promising targets and bioconjugation strategies will aid in driving research in this field forward towards more effective, less toxic, and non- or minimally invasive treatment and diagnosis options for cancer patients. Full article
(This article belongs to the Special Issue Bioconjugation Strategies in Drug Delivery and Molecular Imaging)
►▼ Show Figures

Figure 1

54 pages, 17606 KiB  
Review
Chemistry and Biological Activities of 1,2,4-Triazolethiones—Antiviral and Anti-Infective Drugs
by Ashraf A. Aly, Alaa A. Hassan, Maysa M. Makhlouf and Stefan Bräse
Molecules 2020, 25(13), 3036; https://0-doi-org.brum.beds.ac.uk/10.3390/molecules25133036 - 03 Jul 2020
Cited by 43 | Viewed by 5653
Abstract
Mercapto-substituted 1,2,4-triazoles are very interesting compounds as they play an important role in chemopreventive and chemotherapeutic effects on cancer. In recent decades, literature has been enriched with sulfur- and nitrogen-containing heterocycles which are used as a basic nucleus of different heterocyclic compounds with [...] Read more.
Mercapto-substituted 1,2,4-triazoles are very interesting compounds as they play an important role in chemopreventive and chemotherapeutic effects on cancer. In recent decades, literature has been enriched with sulfur- and nitrogen-containing heterocycles which are used as a basic nucleus of different heterocyclic compounds with various biological applications in medicine and also occupy a huge part of natural products. Therefore, we shed, herein, more light on the synthesis of this interesting class and its application as a biologically active moiety. They might also be suitable as antiviral and anti-infective drugs. Full article
(This article belongs to the Special Issue Bioconjugation Strategies in Drug Delivery and Molecular Imaging)
►▼ Show Figures

Figure 1

Show export options expand_more Show export options expand_less
Select all
Export citation of selected articles as:
 
Displaying articles 1-24
Back to TopTop