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Delivery of Molecules Using Nanoscale Systems for Cancer Treatment and/or...
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Delivery of Molecules Using Nanoscale Systems for Cancer Treatment and/or Diagnosis

A special issue of Pharmaceutics (ISSN 1999-4923). This special issue belongs to the section "Drug Delivery and Controlled Release".

Deadline for manuscript submissions: closed (10 December 2021) | Viewed by 39980

Printed Edition Available!
A printed edition of this Special Issue is available here.

Special Issue Editors

Dr. Marina Santiago Franco

E-Mail Website
Guest Editor
1. Institute of Radiation Medicine (IRM), Department of Radiation Sciences (DRS), Helmholtz Zentrum München, 85764 Neuherberg, Germany
2. Department of Radiation Oncology, School of Medicine, Technical University of Munich (TUM), Klinikum rechts der Isar, 81675 Munich, Germany
Interests: cancer; drug delivery; nanosystems; liposomes; chemotherapy; radiotherapy; microbeams; abscopal effect
Special Issues, Collections and Topics in MDPI journals
Prof. Dr. Yu Seok Youn

E-Mail Website
Guest Editor
School of Pharmacy, Sungkyunkwan University, Suwon 440-746, Gyeonggi-do, Republic of Korea
Interests: cancer nanomedicines; targeted drug delivery; pulmonary drug delivery system; sustained release microparticles; nanoparticle manufacturing

Special Issue Information

Dear Colleagues,

Since the clinical approval of the first liposomal formulation encapsulating a chemotherapeutic agent, nanoscale delivery systems designed for cancer treatment and diagnosis are a rapidly developing science. This delivery strategy is evolving and more recently, the co-delivery of anticancer agent combinations allows the targeting of different pathways, genes, or cell cycle checkpoints so that resistance to single agents can be overcome. Multiple studies in this field have shown the potential of simultaneous release of different agents to the tumor site. Not only that, but also the possibility to control the delivered ratios of these agents, improving synergistic antitumor effects. Meanwhile, the co-delivery of an anticancer agent and a medical imaging agent allows simultaneous cancer therapy and imaging, significantly improving cancer management. These approaches are often further combined to strategies such as active targeting or triggered delivery, culminating in highly multifunctional nanoscale systems. 

This Special Issue will highlight current advances and challenges in the broad theme of nanosystem development for the delivery of molecules to treat and/or diagnose tumors. We encourage the submission of focused review manuscripts as well as original research concerning in vitro, in vivo, and translational studies.

Dr. Marina Santiago Franco
Prof. Dr. Yu Seok Youn
Guest Editors

Manuscript Submission Information

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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. Pharmaceutics is an international peer-reviewed open access monthly 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 2900 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

  • delivery
  • nanosystems
  • cancer
  • combination chemotherapy
  • anticancer agents
  • co-encapsulation
  • ratiometric drug delivery
  • synergism
  • cancer diagnosis
  • imaging agents
  • theranostics

Published Papers (15 papers)

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Editorial

Jump to: Research, Review

3 pages, 181 KiB  
Editorial
Delivery of Molecules Using Nanoscale Systems for Cancer Treatment and/or Diagnosis
by Marina Santiago Franco and Yu Seok Youn
Pharmaceutics 2022, 14(4), 851; https://0-doi-org.brum.beds.ac.uk/10.3390/pharmaceutics14040851 - 13 Apr 2022
Viewed by 1099
Abstract
Since clinical approval of the first liposomal formulation encapsulating a chemotherapeutic agent, nanoscale delivery systems have been a rapidly developing science [...] Full article
(This article belongs to the Special Issue Delivery of Molecules Using Nanoscale Systems for Cancer Treatment and/or Diagnosis)

Research

Jump to: Editorial, Review

20 pages, 59247 KiB  
Article
Combined Antitumor Therapy Using In Situ Injectable Hydrogels Formulated with Albumin Nanoparticles Containing Indocyanine Green, Chlorin e6, and Perfluorocarbon in Hypoxic Tumors
by Woo Tak Lee, Johyun Yoon, Sung Soo Kim, Hanju Kim, Nguyen Thi Nguyen, Xuan Thien Le, Eun Seong Lee, Kyung Taek Oh, Han-Gon Choi and Yu Seok Youn
Pharmaceutics 2022, 14(1), 148; https://0-doi-org.brum.beds.ac.uk/10.3390/pharmaceutics14010148 - 08 Jan 2022
Cited by 14 | Viewed by 2701
Abstract
Combined therapy using photothermal and photodynamic treatments together with chemotherapeutic agents is considered one of the most synergistic treatment protocols to ablate hypoxic tumors. Herein, we sought to fabricate an in situ-injectable PEG hydrogel system having such multifunctional effects. This PEG hydrogel was [...] Read more.
Combined therapy using photothermal and photodynamic treatments together with chemotherapeutic agents is considered one of the most synergistic treatment protocols to ablate hypoxic tumors. Herein, we sought to fabricate an in situ-injectable PEG hydrogel system having such multifunctional effects. This PEG hydrogel was prepared with (i) nabTM-technique-based paclitaxel (PTX)-bound albumin nanoparticles with chlorin-e6 (Ce6)-conjugated bovine serum albumin (BSA-Ce6) and indocyanine green (ICG), named ICG/PTX/BSA-Ce6-NPs (~175 nm), and (ii) an albumin-stabilized perfluorocarbon (PFC) nano-emulsion (BSA-PFC-NEs; ~320 nm). This multifunctional PEG hydrogel induced moderate and severe hyperthermia (41−42 °C and >48 °C, respectively) at the target site under two different 808 nm laser irradiation protocols, and also induced efficient singlet oxygen (1O2) generation under 660 nm laser irradiation supplemented by oxygen produced by ultrasound-triggered PFC. Due to such multifunctionality, our PEG hydrogel formula displayed significantly enhanced killing of three-dimensional 4T1 cell spheroids and also suppressed the growth of xenografted 4T1 cell tumors in mice (tumor volume: 47.7 ± 11.6 and 63.4 ± 13.0 mm3 for photothermal and photodynamic treatment, respectively, vs. PBS group (805.9 ± 138.5 mm3), presumably based on sufficient generation of moderate heat as well as 1O2/O2 even under hypoxic conditions. Our PEG hydrogel formula also showed excellent hyperthermal efficacy (>50 °C), ablating the 4T1 tumors when the irradiation duration was extended and output intensity was increased. We expect that our multifunctional PEG hydrogel formula will become a prototype for ablation of otherwise poorly responsive hypoxic tumors. Full article
(This article belongs to the Special Issue Delivery of Molecules Using Nanoscale Systems for Cancer Treatment and/or Diagnosis)
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21 pages, 6299 KiB  
Article
Novel Selectively Targeted Multifunctional Nanostructured Lipid Carriers for Prostate Cancer Treatment
by Lital Cohen, Yehuda G. Assaraf and Yoav D. Livney
Pharmaceutics 2022, 14(1), 88; https://0-doi-org.brum.beds.ac.uk/10.3390/pharmaceutics14010088 - 30 Dec 2021
Cited by 11 | Viewed by 2322
Abstract
Prostate cancer (PC) is the most common cancer in men over 50 and the 4th most prevalent human malignancy. PC treatment may include surgery, androgen deprivation therapy, chemotherapy, and radiation therapy. However, the therapeutic efficacy of systemic chemotherapy is limited due to low [...] Read more.
Prostate cancer (PC) is the most common cancer in men over 50 and the 4th most prevalent human malignancy. PC treatment may include surgery, androgen deprivation therapy, chemotherapy, and radiation therapy. However, the therapeutic efficacy of systemic chemotherapy is limited due to low drug solubility and insufficient tumor specificity, inflicting toxic side effects and frequently provoking the emergence of drug resistance. Towards the efficacious treatment of PC, we herein developed novel selectively PC-targeted nanoparticles (NPs) harboring a cytotoxic drug cargo. This delivery system is based upon PEGylated nanostructured lipid carriers (NLCs), decorated with a selective ligand, targeted to prostate-specific membrane antigen (PSMA). NPs loaded with cabazitaxel (CTX) displayed a remarkable loading capacity of 168 ± 3 mg drug/g SA-PEG, encapsulation efficiency of 67 ± 1%, and an average diameter of 159 ± 3 nm. The time-course of in vitro drug release from NPs revealed a substantial drug retention profile compared to the unencapsulated drug. These NPs were selectively internalized into target PC cells overexpressing PSMA, and displayed a dose-dependent growth inhibition compared to cells devoid of the PSMA receptor. Remarkably, these targeted NPs exhibited growth-inhibitory activity at pM CTX concentrations, being markedly more potent than the free drug. This selectively targeted nano-delivery platform bears the promise of enhanced efficacy and minimal untoward toxicity. Full article
(This article belongs to the Special Issue Delivery of Molecules Using Nanoscale Systems for Cancer Treatment and/or Diagnosis)
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13 pages, 3927 KiB  
Article
Cathepsin B-Overexpressed Tumor Cell Activatable Albumin-Binding Doxorubicin Prodrug for Cancer-Targeted Therapy
by Hanhee Cho, Man Kyu Shim, Suah Yang, Sukyung Song, Yujeong Moon, Jinseong Kim, Youngro Byun, Cheol-Hee Ahn and Kwangmeyung Kim
Pharmaceutics 2022, 14(1), 83; https://0-doi-org.brum.beds.ac.uk/10.3390/pharmaceutics14010083 - 29 Dec 2021
Cited by 14 | Viewed by 2978
Abstract
Prodrugs are bioreversible medications that should undergo an enzymatic or chemical transformation in the tumor microenvironment to release active drugs, which improve cancer selectivity to reduce toxicities of anticancer drugs. However, such approaches have been challenged by poor therapeutic efficacy attributed to a [...] Read more.
Prodrugs are bioreversible medications that should undergo an enzymatic or chemical transformation in the tumor microenvironment to release active drugs, which improve cancer selectivity to reduce toxicities of anticancer drugs. However, such approaches have been challenged by poor therapeutic efficacy attributed to a short half-life and low tumor targeting. Herein, we propose cathepsin B-overexpressed tumor cell activatable albumin-binding doxorubicin prodrug, Al-ProD, that consists of a albumin-binding maleimide group, cathepsin B-cleavable peptide (FRRG), and doxorubicin. The Al-ProD binds to in situ albumin, and albumin-bound Al-ProD indicates high tumor accumulation with prolonged half-life, and selctively releases doxorubicin in cathepsin B-overexpressed tumor cells, inducing a potent antitumor efficacy. Concurrently, toxicity of Al-ProD toward normal tissues with innately low cathepsin B expression is significantly reduced by maintaining an inactive state, thereby increasing the safety of chemotherapy. This study offers a promising approach for effective and safe chemotherapy, which may open new avenues for drug design and translational medicine. Full article
(This article belongs to the Special Issue Delivery of Molecules Using Nanoscale Systems for Cancer Treatment and/or Diagnosis)
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19 pages, 2323 KiB  
Article
Sulfonated Amphiphilic Poly(α)glutamate Amine—A Potential siRNA Nanocarrier for the Treatment of Both Chemo-Sensitive and Chemo-Resistant Glioblastoma Tumors
by Adva Krivitsky, Sabina Pozzi, Eilam Yeini, Sahar Israeli Dangoor, Tal Zur, Sapir Golan, Vadim Krivitsky, Nitzan Albeck, Evgeny Pisarevsky, Paula Ofek, Asaf Madi and Ronit Satchi-Fainaro
Pharmaceutics 2021, 13(12), 2199; https://0-doi-org.brum.beds.ac.uk/10.3390/pharmaceutics13122199 - 20 Dec 2021
Cited by 2 | Viewed by 2878
Abstract
Development of chemo-resistance is a major challenge in glioblastoma (GB) treatment. This phenomenon is often driven by increased activation of genes associated with DNA repair, such as the alkyl-removing enzyme O6-methylguanine-DNA methyltransferase (MGMT) in combination with overexpression of canonical genes related [...] Read more.
Development of chemo-resistance is a major challenge in glioblastoma (GB) treatment. This phenomenon is often driven by increased activation of genes associated with DNA repair, such as the alkyl-removing enzyme O6-methylguanine-DNA methyltransferase (MGMT) in combination with overexpression of canonical genes related to cell proliferation and tumor progression, such as Polo-like kinase 1 (Plk1). Hereby, we attempt to sensitize resistant GB cells using our established amphiphilic poly(α)glutamate (APA): small interfering RNA (siRNA) polyplexes, targeting Plk1. Furthermore, we improved brain-targeting by decorating our nanocarrier with sulfonate groups. Our sulfonated nanocarrier showed superior selectivity towards P-selectin (SELP), a transmembrane glycoprotein overexpressed in GB and angiogenic brain endothelial cells. Self-assembled polyplexes of sulfonated APA and siPlk1 internalized into GB cells and into our unique 3-dimensional (3D) GB spheroids inducing specific gene silencing. Moreover, our RNAi nanotherapy efficiently reduced the cell viability of both chemo-sensitive and chemo-resistant GB cells. Our developed sulfonated amphiphilic poly(α)glutamate nanocarrier has the potential to target siRNA to GB brain tumors. Our findings may strengthen the therapeutic applications of siRNA for chemo-resistant GB tumors, or as a combination therapy for chemo-sensitive GB tumors. Full article
(This article belongs to the Special Issue Delivery of Molecules Using Nanoscale Systems for Cancer Treatment and/or Diagnosis)
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15 pages, 3649 KiB  
Article
Antigen-Capturing Mesoporous Silica Nanoparticles Enhance the Radiation-Induced Abscopal Effect in Murine Hepatocellular Carcinoma Hepa1-6 Models
by Kyungmi Yang, Changhoon Choi, Hayeong Cho, Won-Gyun Ahn, Shin-Yeong Kim, Sung-Won Shin, Yeeun Kim, Taekyu Jang, Nohyun Lee and Hee Chul Park
Pharmaceutics 2021, 13(11), 1811; https://0-doi-org.brum.beds.ac.uk/10.3390/pharmaceutics13111811 - 29 Oct 2021
Cited by 8 | Viewed by 2661
Abstract
Immunomodulation by radiotherapy (RT) is an emerging strategy for improving cancer immunotherapy. Nanomaterials have been employed as innovative tools for cancer therapy. This study aimed to investigate whether mesoporous silica nanoparticles (MSNs) enhance RT-mediated local tumor control and the abscopal effect by stimulating [...] Read more.
Immunomodulation by radiotherapy (RT) is an emerging strategy for improving cancer immunotherapy. Nanomaterials have been employed as innovative tools for cancer therapy. This study aimed to investigate whether mesoporous silica nanoparticles (MSNs) enhance RT-mediated local tumor control and the abscopal effect by stimulating anti-cancer immunity. Hepa1-6 murine hepatocellular carcinoma syngeneic models and immunophenotyping with flow cytometry were used to evaluate the immune responses. When mice harboring bilateral tumors received 8 Gy of X-rays on a single tumor, the direct injection of MSNs into irradiated tumors enhanced the growth inhibition of irradiated and unirradiated contralateral tumors. MSNs enhanced RT-induced tumor infiltration of cytotoxic T cells on both sides and suppressed RT-enhanced infiltration of regulatory T cells. The administration of MSNs pre-incubated with irradiated cell-conditioned medium enhanced the anti-tumor effect of anti-PD1 compared to the as-synthesized MSNs. Intracellular uptake of MSNs activated JAWS II dendritic cells (DCs), which were consistently observed in DCs in tumor-draining lymph nodes (TDLNs). Our findings suggest that MSNs may capture tumor antigens released after RT, which is followed by DC maturation in TDLNs and infiltration of cytotoxic T cells in tumors, thereby leading to systemic tumor regression. Our results suggest that MSNs can be applied as an adjuvant for in situ cancer vaccines with RT. Full article
(This article belongs to the Special Issue Delivery of Molecules Using Nanoscale Systems for Cancer Treatment and/or Diagnosis)
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15 pages, 2459 KiB  
Article
AS1411 Aptamer Linked to DNA Nanostructures Diverts Its Traffic Inside Cancer Cells and Improves Its Therapeutic Efficacy
by Giulia Vindigni, Sofia Raniolo, Federico Iacovelli, Valeria Unida, Carmine Stolfi, Alessandro Desideri and Silvia Biocca
Pharmaceutics 2021, 13(10), 1671; https://0-doi-org.brum.beds.ac.uk/10.3390/pharmaceutics13101671 - 13 Oct 2021
Cited by 18 | Viewed by 2444
Abstract
The nucleolin-binding G-quadruplex AS1411 aptamer has been widely used for cancer therapy and diagnosis and linked to nanoparticles for its selective targeting activity. We applied a computational and experimental integrated approach to study the effect of engineering AS1411 aptamer on an octahedral truncated [...] Read more.
The nucleolin-binding G-quadruplex AS1411 aptamer has been widely used for cancer therapy and diagnosis and linked to nanoparticles for its selective targeting activity. We applied a computational and experimental integrated approach to study the effect of engineering AS1411 aptamer on an octahedral truncated DNA nanocage to obtain a nanostructure able to combine selective cancer-targeting and anti-tumor activity. The nanocages functionalized with one aptamer molecule (Apt-NC) displayed high stability in serum, were rapidly and selectively internalized in cancer cells through an AS1411-dependent mechanism, and showed over 200-fold increase in anti-cancer activity when compared with the free aptamer. Comparison of Apt-NCs and free AS1411 intracellular distribution showed that they traffic differently inside cells: Apt-NCs distributed through the endo-lysosomal pathway and were never found in the nuclei, while the free AS1411 was mostly found in the perinuclear region and in nucleoli. Molecular dynamics simulations indicated that the aptamer, when linked to the nanocage, sampled a limited conformational space, more confined than in the free state, which is characterized by a large number of metastable conformations. A different intracellular trafficking of Apt-NCs compared with free aptamer and the confined aptamer conformations induced by the nanocage were likely correlated with the high cytotoxic enhancement, suggesting a structure–function relationship for the AS1411 aptamer activity. Full article
(This article belongs to the Special Issue Delivery of Molecules Using Nanoscale Systems for Cancer Treatment and/or Diagnosis)
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Graphical abstract

20 pages, 6615 KiB  
Article
Targeting Tumor Cells with Nanoparticles for Enhanced Co-Drug Delivery in Cancer Treatment
by Wen-Ying Huang, Chih-Ho Lai, Shin-Lei Peng, Che-Yu Hsu, Po-Hung Hsu, Pei-Yi Chu, Chun-Lung Feng and Yu-Hsin Lin
Pharmaceutics 2021, 13(9), 1327; https://0-doi-org.brum.beds.ac.uk/10.3390/pharmaceutics13091327 - 25 Aug 2021
Cited by 8 | Viewed by 2530
Abstract
Gastric cancer (GC) is a fatal malignant tumor, and effective therapies to attenuate its progression are lacking. Nanoparticle (NP)-based solutions may enable the design of novel treatments to eliminate GC. Refined, receptor-targetable NPs can selectively target cancer cells and improve the cellular uptake [...] Read more.
Gastric cancer (GC) is a fatal malignant tumor, and effective therapies to attenuate its progression are lacking. Nanoparticle (NP)-based solutions may enable the design of novel treatments to eliminate GC. Refined, receptor-targetable NPs can selectively target cancer cells and improve the cellular uptake of drugs. To overcome the current limitations and enhance the therapeutic effects, epigallocatechin-3-gallate (EGCG) and low-concentration doxorubicin (DX) were encapsulated in fucoidan and d-alpha-tocopherylpoly (ethylene glycol) succinate-conjugated hyaluronic acid-based NPs for targeting P-selectin-and cluster of differentiation (CD)44-expressing gastric tumors. The EGCG/DX-loaded NPs bound to GC cells and released bioactive combination drugs, demonstrating better anti-cancer effects than the EGCG/DX combination solution. In vivo assays in an orthotopic gastric tumor mouse model showed that the EGCG/DX-loaded NPs significantly increased the activity of gastric tumors without inducing organ injury. Overall, our EGCG/DX-NP system exerted a beneficial effect on GC treatment and may facilitate the development of nanomedicine-based combination chemotherapy against GC in the future. Full article
(This article belongs to the Special Issue Delivery of Molecules Using Nanoscale Systems for Cancer Treatment and/or Diagnosis)
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Graphical abstract

16 pages, 5407 KiB  
Article
Modification of Proliferation and Apoptosis in Breast Cancer Cells by Exposure of Antioxidant Nanoparticles Due to Modulation of the Cellular Redox State Induced by Doxorubicin Exposure
by Laura Denise López-Barrera, Roberto Díaz-Torres, Joselo Ramón Martínez-Rosas, Ana María Salazar, Carlos Rosales and Patricia Ramírez-Noguera
Pharmaceutics 2021, 13(8), 1251; https://0-doi-org.brum.beds.ac.uk/10.3390/pharmaceutics13081251 - 13 Aug 2021
Cited by 8 | Viewed by 2027
Abstract
In this report, we investigated whether the use of chitosan-carrying-glutathione nanoparticles (CH-GSH NPs) can modify proliferation and apoptosis, and reduce cell damage induced by doxorubicin on breast cancer cells. Doxorubicin is a widely used antineoplasic agent for the treatment of various types of [...] Read more.
In this report, we investigated whether the use of chitosan-carrying-glutathione nanoparticles (CH-GSH NPs) can modify proliferation and apoptosis, and reduce cell damage induced by doxorubicin on breast cancer cells. Doxorubicin is a widely used antineoplasic agent for the treatment of various types of cancer. However, it is also a highly toxic drug because it induces oxidative stress. Thus, the use of antioxidant molecules has been considered to reduce the toxicity of doxorubicin. CH-GSH NPs were characterized in size, zeta potential, concentration, and shape. When breast cancer cells were treated with CH-GSH nanoparticles, they were localized in the cellular cytoplasm. Combined doxorubicin exposure with nanoparticles increased intracellular GSH levels. At the same time, decreasing levels of reactive oxygen species and malondialdehyde were observed and modified antioxidant enzyme activity. Levels of the Ki67 protein were evaluated as a marker of cell proliferation and the activity of the Casp-3 protein related to cell apoptosis was measured. Our data suggests that CH-GSH NPs can modify cell proliferation by decreasing Ki67 levels, induce apoptosis by increasing caspase-3 activity, and reduce the oxidative stress induced by doxorubicin in breast cancer cells by modulating molecules associated with the cellular redox state. CH-GSH NPs could be used to reduce the toxic effects of this antineoplastic. Considering these results, CH-GSH NPs represent a novel delivery system offering new opportunities in pharmacy, material science, and biomedicine. Full article
(This article belongs to the Special Issue Delivery of Molecules Using Nanoscale Systems for Cancer Treatment and/or Diagnosis)
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Graphical abstract

16 pages, 5453 KiB  
Article
Oligoarginine Peptide Conjugated to BSA Improves Cell Penetration of Gold Nanorods and Nanoprisms for Biomedical Applications
by Karen Bolaños, Macarena Sánchez-Navarro, Andreas Tapia-Arellano, Ernest Giralt, Marcelo J. Kogan and Eyleen Araya
Pharmaceutics 2021, 13(8), 1204; https://0-doi-org.brum.beds.ac.uk/10.3390/pharmaceutics13081204 - 05 Aug 2021
Cited by 9 | Viewed by 3059
Abstract
Gold nanoparticles (AuNPs) have been shown to be outstanding tools for drug delivery and biomedical applications, mainly owing to their colloidal stability, surface chemistry, and photothermal properties. The biocompatibility and stability of nanoparticles can be improved by capping the nanoparticles with endogenous proteins, [...] Read more.
Gold nanoparticles (AuNPs) have been shown to be outstanding tools for drug delivery and biomedical applications, mainly owing to their colloidal stability, surface chemistry, and photothermal properties. The biocompatibility and stability of nanoparticles can be improved by capping the nanoparticles with endogenous proteins, such as albumin. Notably, protein coating of nanoparticles can interfere with and decrease their cell penetration. Therefore, in the present study, we functionalized albumin with the r8 peptide (All-D, octaarginine) and used it for coating NIR-plasmonic anisotropic gold nanoparticles. Gold nanoprisms (AuNPrs) and gold nanorods (AuNRs) were coated with bovine serum albumin (BSA) previously functionalized using a cell penetrating peptide (CPP) with the r8 sequence (BSA-r8). The effect of the coated and r8-functionalized AuNPs on HeLa cell viability was assessed by the MTS assay, showing a low effect on cell viability after BSA coating. Moreover, the internalization of the nanostructures into HeLa cells was assessed by confocal microscopy and transmission electron microscopy (TEM). As a result, both nanoconstructs showed an improved internalization level after being capped with BSA-r8, in contrast to the BSA-functionalized control, suggesting the predominant role of CPP functionalization in cell internalization. Thus, our results validate both novel nanoconstructs as potential candidates to be coated by endogenous proteins and functionalized with a CPP to optimize cell internalization. In a further approach, coating AuNPs with CPP-functionalized BSA can broaden the possibilities for biomedical applications by combining their optical properties, biocompatibility, and cell-penetration abilities. Full article
(This article belongs to the Special Issue Delivery of Molecules Using Nanoscale Systems for Cancer Treatment and/or Diagnosis)
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18 pages, 2693 KiB  
Article
Nanoencapsulated Doxorubicin Prevents Mucositis Development in Mice
by Cristiane M. Pinto, Laila S. Horta, Amanda P. Soares, Bárbara A. Carvalho, Enio Ferreira, Eduardo B. Lages, Lucas A. M. Ferreira, André A. G. Faraco, Helton C. Santiago and Gisele A. C. Goulart
Pharmaceutics 2021, 13(7), 1021; https://0-doi-org.brum.beds.ac.uk/10.3390/pharmaceutics13071021 - 04 Jul 2021
Cited by 17 | Viewed by 2824
Abstract
Doxorubicin (DOX), a chemotherapy drug successfully used in the therapy of various types of cancer, is currently associated with the mucositis development, an inflammation that can cause ulcerative lesions in the mucosa of the gastrointestinal tract, abdominal pain and secondary infections. To increase [...] Read more.
Doxorubicin (DOX), a chemotherapy drug successfully used in the therapy of various types of cancer, is currently associated with the mucositis development, an inflammation that can cause ulcerative lesions in the mucosa of the gastrointestinal tract, abdominal pain and secondary infections. To increase the safety of the chemotherapy, we loaded DOX into nanostructured lipid carriers (NLCs). The NLC–DOX was characterized by HPLC, DLS, NTA, Zeta potential, FTIR, DSC, TEM and cryogenic-TEM. The ability of NLC–DOX to control the DOX release was evaluated through in vitro release studies. Moreover, the effect of NLC–DOX on intestinal mucosa was compared to a free DOX solution in C57BL/6 mice. The NLC–DOX showed spherical shape, high drug encapsulation efficiency (84.8 ± 4.6%), high drug loading (55.2 ± 3.4 mg/g) and low average diameter (66.0–78.8 nm). The DSC and FTIR analyses showed high interaction between the NLC components, resulting in controlled drug release. Treatment with NLC–DOX attenuated DOX-induced mucositis in mice, improving shortening on villus height and crypt depth, decreased inflammatory parameters, preserved intestinal permeability and increased expression of tight junctions (ZO-1 and Ocludin). These results indicated that encapsulation of DOX in NLCs is viable and reduces the drug toxicity to mucosal structures. Full article
(This article belongs to the Special Issue Delivery of Molecules Using Nanoscale Systems for Cancer Treatment and/or Diagnosis)
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Review

Jump to: Editorial, Research

24 pages, 1373 KiB  
Review
Combining Nanocarrier-Assisted Delivery of Molecules and Radiotherapy
by Eliza Rocha Gomes and Marina Santiago Franco
Pharmaceutics 2022, 14(1), 105; https://0-doi-org.brum.beds.ac.uk/10.3390/pharmaceutics14010105 - 03 Jan 2022
Cited by 4 | Viewed by 1985
Abstract
Cancer is responsible for a significant proportion of death all over the world. Therefore, strategies to improve its treatment are highly desired. The use of nanocarriers to deliver anticancer treatments has been extensively investigated and improved since the approval of the first liposomal [...] Read more.
Cancer is responsible for a significant proportion of death all over the world. Therefore, strategies to improve its treatment are highly desired. The use of nanocarriers to deliver anticancer treatments has been extensively investigated and improved since the approval of the first liposomal formulation for cancer treatment in 1995. Radiotherapy (RT) is present in the disease management strategy of around 50% of cancer patients. In the present review, we bring the state-of-the-art information on the combination of nanocarrier-assisted delivery of molecules and RT. We start with formulations designed to encapsulate single or multiple molecules that, once delivered to the tumor site, act directly on the cells to improve the effects of RT. Then, we describe formulations designed to modulate the tumor microenvironment by delivering oxygen or to boost the abscopal effect. Finally, we present how RT can be employed to trigger molecule delivery from nanocarriers or to modulate the EPR effect. Full article
(This article belongs to the Special Issue Delivery of Molecules Using Nanoscale Systems for Cancer Treatment and/or Diagnosis)
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28 pages, 1388 KiB  
Review
Phthalocyanine and Its Formulations: A Promising Photosensitizer for Cervical Cancer Phototherapy
by Lucimara R. Carobeli, Lyvia E. de F. Meirelles, Gabrielle M. Z. F. Damke, Edilson Damke, Maria V. F. de Souza, Natália L. Mari, Kayane H. Mashiba, Cristiane S. Shinobu-Mesquita, Raquel P. Souza, Vânia R. S. da Silva, Renato S. Gonçalves, Wilker Caetano and Márcia E. L. Consolaro
Pharmaceutics 2021, 13(12), 2057; https://0-doi-org.brum.beds.ac.uk/10.3390/pharmaceutics13122057 - 02 Dec 2021
Cited by 11 | Viewed by 3068
Abstract
Cervical cancer is one of the most common causes of cancer-related deaths in women worldwide. Despite advances in current therapies, women with advanced or recurrent disease present poor prognosis. Photodynamic therapy (PDT) has emerged as an effective therapeutic alternative to treat oncological diseases [...] Read more.
Cervical cancer is one of the most common causes of cancer-related deaths in women worldwide. Despite advances in current therapies, women with advanced or recurrent disease present poor prognosis. Photodynamic therapy (PDT) has emerged as an effective therapeutic alternative to treat oncological diseases such as cervical cancer. Phthalocyanines (Pcs) are considered good photosensitizers (PS) for PDT, although most of them present high levels of aggregation and are lipophilic. Despite many investigations and encouraging results, Pcs have not been approved as PS for PDT of invasive cervical cancer yet. This review presents an overview on the pathophysiology of cervical cancer and summarizes the most recent developments on the physicochemical properties of Pcs and biological results obtained both in vitro in tumor-bearing mice and in clinical tests reported in the last five years. Current evidence indicates that Pcs have potential as pharmaceutical agents for anti-cervical cancer therapy. The authors firmly believe that Pc-based formulations could emerge as a privileged scaffold for the establishment of lead compounds for PDT against different types of cervical cancer. Full article
(This article belongs to the Special Issue Delivery of Molecules Using Nanoscale Systems for Cancer Treatment and/or Diagnosis)
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41 pages, 3002 KiB  
Review
Progress in Nanocarriers Codelivery System to Enhance the Anticancer Effect of Photodynamic Therapy
by Yu-Ling Yang, Ke Lin and Li Yang
Pharmaceutics 2021, 13(11), 1951; https://0-doi-org.brum.beds.ac.uk/10.3390/pharmaceutics13111951 - 18 Nov 2021
Cited by 15 | Viewed by 2876
Abstract
Photodynamic therapy (PDT) is a promising anticancer noninvasive method and has great potential for clinical applications. Unfortunately, PDT still has many limitations, such as metastatic tumor at unknown sites, inadequate light delivery and a lack of sufficient oxygen. Recent studies have demonstrated that [...] Read more.
Photodynamic therapy (PDT) is a promising anticancer noninvasive method and has great potential for clinical applications. Unfortunately, PDT still has many limitations, such as metastatic tumor at unknown sites, inadequate light delivery and a lack of sufficient oxygen. Recent studies have demonstrated that photodynamic therapy in combination with other therapies can enhance anticancer effects. The development of new nanomaterials provides a platform for the codelivery of two or more therapeutic drugs, which is a promising cancer treatment method. The use of multifunctional nanocarriers for the codelivery of two or more drugs can improve physical and chemical properties, increase tumor site aggregation, and enhance the antitumor effect through synergistic actions, which is worthy of further study. This review focuses on the latest research progress on the synergistic enhancement of PDT by simultaneous multidrug administration using codelivery nanocarriers. We introduce the design of codelivery nanocarriers and discuss the mechanism of PDT combined with other antitumor methods. The combination of PDT and chemotherapy, gene therapy, immunotherapy, photothermal therapy, hyperthermia, radiotherapy, sonodynamic therapy and even multidrug therapy are discussed to provide a comprehensive understanding. Full article
(This article belongs to the Special Issue Delivery of Molecules Using Nanoscale Systems for Cancer Treatment and/or Diagnosis)
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16 pages, 2653 KiB  
Review
Magnetofection In Vivo by Nanomagnetic Carriers Systemically Administered into the Bloodstream
by Artem A. Sizikov, Petr I. Nikitin and Maxim P. Nikitin
Pharmaceutics 2021, 13(11), 1927; https://0-doi-org.brum.beds.ac.uk/10.3390/pharmaceutics13111927 - 14 Nov 2021
Cited by 12 | Viewed by 2234
Abstract
Nanoparticle-based technologies are rapidly expanding into many areas of biomedicine and molecular science. The unique ability of magnetic nanoparticles to respond to the magnetic field makes them especially attractive for a number of in vivo applications including magnetofection. The magnetofection principle consists of [...] Read more.
Nanoparticle-based technologies are rapidly expanding into many areas of biomedicine and molecular science. The unique ability of magnetic nanoparticles to respond to the magnetic field makes them especially attractive for a number of in vivo applications including magnetofection. The magnetofection principle consists of the accumulation and retention of magnetic nanoparticles carrying nucleic acids in the area of magnetic field application. The method is highly promising as a clinically efficient tool for gene delivery in vivo. However, the data on in vivo magnetofection are often only descriptive or poorly studied, insufficiently systematized, and sometimes even contradictory. Therefore, the aim of the review was to systematize and analyze the data that influence the in vivo magnetofection processes after the systemic injection of magnetic nanostructures. The main emphasis is placed on the structure and coating of the nanomagnetic vectors. The present problems and future trends of the method development are also considered. Full article
(This article belongs to the Special Issue Delivery of Molecules Using Nanoscale Systems for Cancer Treatment and/or Diagnosis)
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