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Nanostructures Applied to Drug Delivery and Diagnosis

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A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Macromolecules".

Deadline for manuscript submissions: closed (15 June 2021) | Viewed by 17830

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Dr. Olga Abian

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Guest Editor

Instituto Aragonés de Ciencias de la Salud (IACS)
Interests: Clinical Diagnosis (Thermal Liquid Biopsy (TLB); serum sample; differential scanning calorimetry (DSC); Cancer Screening Programs; Early diagnostic and prognostic), Drug Delivery (Dendrimers; Drug carriers; Self-assembly; Micelles); Protein target and Drug design (Intrinsically disordered proteins (IDPs); Experimental molecular screening; Fluorescence Thermal Shift; Ligand-induced stabilization; Protein stability; Conformational disease; Pharmacological chaperone; Infectious disease; Isothermal titration calorimetry (ITC))

Special Issue Information

Dear Colleagues,

Supramolecular self-assembly has recently attracted the attention of researchers worldwide in generating nanostructures and nanomaterials bearing unique physical and chemical properties. Synthetic molecules such as amino acids, oligo- and polypeptides, polymers, dendrimers, and π-conjugated compounds have been considered as the primary focus used for building up nanostructures, such as nanotubes, nanofibers, micelles, and vesicles.

Furthermore, self-assembly of small molecules as building units is a useful strategy for the formation of structure-controlled materials because of their unique properties, including controlled architecture, versatile functionalization and cargo, and transport and release of diverse molecules. The architecture and chemical structure of the final nanostructure together with its terminal groups defines the interaction with cargo molecules and also their efficient uptake by host cells.

In the case of drug delivery, these nanostructures have been extensively investigated as drug and DNA carriers for cancer-related biomedical applications. Another potential biomedical application of these nanostructures is related to clinical diagnosis. Taking advantage of their characteristics, it is possible to identify specific biomarkers of disease.

For this Special Issue, we are looking for original research articles and state-of-the-art reviews on novel or established self-assembled nanostructures that could be applied in clinics, either as drug carriers or biomarker sensors.

Dr. Olga Abian
Guest Editor

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Published Papers (6 papers)

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Research

19 pages, 29349 KiB

Open AccessArticle

Poly(amidoamine) Dendrimers as Nanocarriers for 5-Fluorouracil: Effectiveness of Complex Formation and Cytotoxicity Studies

by Magdalena Szota, Katarzyna Reczyńska-Kolman, Elżbieta Pamuła, Olga Michel, Julita Kulbacka and Barbara Jachimska

Int. J. Mol. Sci. 2021, 22(20), 11167; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms222011167 - 16 Oct 2021

Cited by 6 | Viewed by 2183

Abstract

Two generations of positively charged poly(amidoamine) dendrimers (PAMAMs) were selected for study as potential carriers for the anticancer drug 5-fluorouracil (5FU), a drug primarily used in the treatment of colorectal cancer. Analytical techniques, such as UV-Vis spectrophotometry, NMR Spectroscopy and Laser Doppler Velocimetry (LDV), have shown that the most critical factor determining the formation of a PAMAM–5FU complex is the starting components’ protonation degree. The tests confirmed the system’s ability to attach about 20 5FU molecules per one dendrimer molecule for the G4PAMAM dendrimer and about 25 molecules for the G6PAMAM dendrimer, which gives a system yield of 16% for the fourth generation and 5% for sixth generation dendrimers. Additionally, using the QCM-D method, the adsorption efficiency and the number of drug molecules immobilized in the dendrimer structure were determined. A new aspect in our study was the determination of the change in zeta potential (ζ) induced by the immobilization of 5FU molecules on the dendrimer’s outer shell and the importance of this effect in the direct contact of the carrier with cells. Cytotoxicity tests (resazurin reduction and MTS tests) showed no toxicity of dendrimers against mouse fibroblast cells (L929) and a significant decrease in cell viability in the case of four human malignant cell lines: malignant melanoma (A375), glioblastoma (SNB-19), prostate cancer (Du-145) and colon adenocarcinoma (HT-29) during incubation with PAMAM–5FU complexes. The purpose of our work was to investigate the correlation between the physicochemical properties of the carrier and active substance and the system efficiency and optimizing conditions for the formation of an efficient system based on PAMAM dendrimers as nanocarriers for 5-fluorouracil. An additional aspect was to identify potential application properties of the complexes, as demonstrated by cytotoxicity tests. Full article

(This article belongs to the Special Issue Nanostructures Applied to Drug Delivery and Diagnosis)

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22 pages, 31291 KiB

Open AccessArticle

Fluorescence Liquid Biopsy for Cancer Detection Is Improved by Using Cationic Dendronized Hyperbranched Polymer

by Violeta Morcuende-Ventura, Sonia Hermoso-Durán, Natalia Abian-Franco, Roberto Pazo-Cid, Jorge L. Ojeda, Sonia Vega, Oscar Sanchez-Gracia, Adrian Velazquez-Campoy, Teresa Sierra and Olga Abian

Int. J. Mol. Sci. 2021, 22(12), 6501; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22126501 - 17 Jun 2021

Cited by 4 | Viewed by 1975

Abstract

(1) Background: Biophysical techniques applied to serum samples characterization could promote the development of new diagnostic tools. Fluorescence spectroscopy has been previously applied to biological samples from cancer patients and differences from healthy individuals were observed. Dendronized hyperbranched polymers (DHP) based on bis(hydroxymethyl)propionic acid (bis-MPA) were developed in our group and their potential biomedical applications explored. (2) Methods: A total of 94 serum samples from diagnosed cancer patients and healthy individuals were studied (20 pancreatic ductal adenocarcinoma, 25 blood donor, 24 ovarian cancer, and 25 benign ovarian cyst samples). (3) Results: Fluorescence spectra of serum samples (fluorescence liquid biopsy, FLB) in the presence and the absence of DHP-bMPA were recorded and two parameters from the signal curves obtained. A secondary parameter, the fluorescence spectrum score (FS_score), was calculated, and the diagnostic model assessed. For pancreatic ductal adenocarcinoma (PDAC) and ovarian cancer, the classification performance was improved when including DHP-bMPA, achieving high values of statistical sensitivity and specificity (over 85% for both pathologies). (4) Conclusions: We have applied FLB as a quick, simple, and minimally invasive promising technique in cancer diagnosis. The classification performance of the diagnostic method was further improved by using DHP-bMPA, which interacted differentially with serum samples from healthy and diseased subjects. These preliminary results set the basis for a larger study and move FLB closer to its clinical application, providing useful information for the oncologist during patient diagnosis. Full article

(This article belongs to the Special Issue Nanostructures Applied to Drug Delivery and Diagnosis)

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19 pages, 2683 KiB

Open AccessArticle

Combination Chemotherapy with Cisplatin and Chloroquine: Effect of Encapsulation in Micelles Formed by Self-Assembling Hybrid Dendritic–Linear–Dendritic Block Copolymers

by Rebeca González-Pastor, Alexandre Lancelot, Violeta Morcuende-Ventura, María San Anselmo, Teresa Sierra, José L. Serrano and Pilar Martin-Duque

Int. J. Mol. Sci. 2021, 22(10), 5223; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22105223 - 14 May 2021

Cited by 10 | Viewed by 2561

Abstract

Clinical outcomes of conventional drug combinations are not ideal due to high toxicity to healthy tissues. Cisplatin (CDDP) is the standard component for many cancer treatments, yet its principal dose-limiting side effect is nephrotoxicity. Thus, CDDP is commonly used in combination with other drugs, such as the autophagy inhibitor chloroquine (CQ), to enhance tumor cell killing efficacy and prevent the development of chemoresistance. In addition, nanocarrier-based drug delivery systems can overcome chemotherapy limitations, decreasing side effects and increasing tumor accumulation. The aim of this study was to evaluate the toxicity of CQ and CDDP against tumor and non-tumor cells when used in a combined treatment. For this purpose, two types of micelles based on Pluronic^® F127 hybrid dendritic–linear–dendritic block copolymers (HDLDBCs) modified with polyester or poly(esteramide) dendrons derived from 2,2′-bis(hydroxymethyl)propionic acid (HDLDBC-bMPA) or 2,2′-bis(glycyloxymethyl)propionic acid (HDLDBC-bGMPA) were explored as delivery nanocarriers. Our results indicated that the combined treatment with HDLDBC-bMPA(CQ) or HDLDBC-bGMPA(CQ) and CDDP increased cytotoxicity in tumor cells compared to the single treatment with CDDP. Encapsulations demonstrated less short-term cytotoxicity individually or when used in combination compared to the free drugs. However, and more importantly, a low degree of cytotoxicity against non-tumor cells was maintained, even when drugs were given simultaneously. Full article

(This article belongs to the Special Issue Nanostructures Applied to Drug Delivery and Diagnosis)

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16 pages, 6087 KiB

Open AccessArticle

Monomethyl Auristatin E Grafted-Liposomes to Target Prostate Tumor Cell Lines

by Ariana Abawi, Xiaoyi Wang, Julien Bompard, Anna Bérot, Valentina Andretto, Leslie Gudimard, Chloé Devillard, Emma Petiot, Benoit Joseph, Giovanna Lollo, Thierry Granjon, Agnès Girard-Egrot and Ofelia Maniti

Int. J. Mol. Sci. 2021, 22(8), 4103; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22084103 - 15 Apr 2021

Cited by 5 | Viewed by 3616

Abstract

Novel nanomedicines have been engineered to deliver molecules with therapeutic potentials, overcoming drawbacks such as poor solubility, toxicity or short half-life. Lipid-based carriers such as liposomes represent one of the most advanced classes of drug delivery systems. A Monomethyl Auristatin E (MMAE) warhead was grafted on a lipid derivative and integrated in fusogenic liposomes, following the model of antibody drug conjugates. By modulating the liposome composition, we designed a set of particles characterized by different membrane fluidities as a key parameter to obtain selective uptake from fibroblast or prostate tumor cells. Only the fluid liposomes made of palmitoyl-oleoyl-phosphatidylcholine and dioleoyl-phosphatidylethanolamine, integrating the MMAE-lipid derivative, showed an effect on prostate tumor PC-3 and LNCaP cell viability. On the other hand, they exhibited negligible effects on the fibroblast NIH-3T3 cells, which only interacted with rigid liposomes. Therefore, fluid liposomes grafted with MMAE represent an interesting example of drug carriers, as they can be easily engineered to promote liposome fusion with the target membrane and ensure drug selectivity. Full article

(This article belongs to the Special Issue Nanostructures Applied to Drug Delivery and Diagnosis)

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17 pages, 3740 KiB

Open AccessArticle

Microemulsion Synthesis of Superparamagnetic Nanoparticles for Bioapplications

by María Salvador, Gemma Gutiérrez, Sara Noriega, Amanda Moyano, María Carmen Blanco-López and María Matos

Int. J. Mol. Sci. 2021, 22(1), 427; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22010427 - 04 Jan 2021

Cited by 46 | Viewed by 4178

Abstract

Superparamagnetic nanoparticles have seen increased potential in medical and environmental applications. Their preparation is traditionally made by the coprecipitation method, with limited control over the particle size distribution. Microemulsion methods could be advantageous due to the efficient control of the size, shape, and composition of the nanoparticles obtained. Water-in-oil (W/O) microemulsions consist of aqueous microdomains dispersed in a continuous oil phase, stabilized by surfactant molecules. These work as nanoreactors where the synthesis of the desired nanoparticles takes place through a co-precipitation chemical reaction. In this work, superparamagnetic magnetite nanoparticles with average diameters between 5.4 and 7.2 nm and large monodispersity have been synthesized through precipitation in a W/O microemulsion, with Cetyl Trimethyl Ammonium Bromide (CTAB) as a main surfactant, 1-butanol as a cosurfactant, and with 1-hexanol as the continuous oily phase. The optimization of the corresponding washing protocol has also been established since a strict control is required when using these materials for bioapplications. Their applicability in those has been proved by their encapsulation in liposomes, being tested as signal enhancers for lateral flow immunoassays by using the affinity neutravidin-biotin model system. Due to their magnetic behaviour, they were also tested for magnetic separation. These novel materials have been found to be useful for analytical applications requiring high sensitivity and the removal of interferences. Full article

(This article belongs to the Special Issue Nanostructures Applied to Drug Delivery and Diagnosis)

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17 pages, 2995 KiB

Open AccessArticle

Linear Copolymers Based on Choline Ionic Liquid Carrying Anti-Tuberculosis Drugs: Influence of Anion Type on Physicochemical Properties and Drug Release

by Katarzyna Niesyto and Dorota Neugebauer

Int. J. Mol. Sci. 2021, 22(1), 284; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22010284 - 30 Dec 2020

Cited by 13 | Viewed by 2472

Abstract

In this study, drug nanocarriers were designed using linear copolymers with different contents of cholinium-based ionic liquid units, i.e., [2-(methacryloyloxy)ethyl]trimethylammonium chloride (TMAMA/Cl: 25, 50, and 75 mol%). The amphiphilicity of the copolymers was evaluated on the basis of their critical micelle concentration (CMC = 0.055–0.079 mg/mL), and their hydrophilicities were determined by water contact angles (WCA = 17°–46°). The chloride anions in the polymer chain were involved in ionic exchange reactions to introduce pharmaceutical anions, i.e., p-aminosalicylate (PAS⁻), clavulanate (CLV⁻), piperacillin (PIP⁻), and fusidate (FUS⁻), which are established antibacterial agents for treating lung and respiratory diseases. The exchange reaction efficiency decreased in the following order: CLV⁻ > PAS⁻ > PIP⁻ >> FUS⁻. The hydrophilicity of the ionic drug conjugates was slightly reduced, as indicated by the increased WCA values. The major fraction of particles with sizes ~20 nm was detected in systems with at least 50% TMAMA carrying PAS or PIP. The influence of the drug character and carrier structure was also observed in the kinetic profiles of the release processes driven by the exchange with phosphate anions (0.5–6.4 μg/mL). The obtained polymer-drug ionic conjugates (especially that with PAS) are promising carriers with potential medical applications. Full article

(This article belongs to the Special Issue Nanostructures Applied to Drug Delivery and Diagnosis)

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