Redox-Responsive Nanoparticles from the Single Disulfide Bond-Bridged Block Copolymer as Drug Carriers for Overcoming Multidrug Resistance in Cancer Cells

Abstract Metal-organic frameworks (MOFs) have proven to be a promising class of drug carriers due to their high porosity, crystalline properties with defined structure information, and their potential for further functionalization. However, to date, no extensive research has been conducted on MOF-based drug carriers with stimuli-responsive, dual-drug delivery, and tumor targeting functions. Here, we demonstrate the strategy of constructing a redox responsive and tumor-targeted MOF, as dual-drug carrier, by anchoring functional disulfide anhydride and folic acid (FA) molecules to the organic links of MOFs, respectively. The MOF composites show the controlled release of loaded 5-fluorouracil (5-FU) entrapped within UiO-66-NH2 nanostructures modified by dichloroacetic acid (DCA). Moreover, the MOF building block DCA acts as a synergistical drug to 5-FU in cancer cells inhibition. Through disulfide bonds, the gated MOF has redox-responsive drugs release. The confocal laser scanning microscopy further proved that conjugation of folic acid to the MOF surface can significantly enhance the targeting ability to cancer cells and the cancer cell uptake of FA-MOFs. The synthesis of redox-responsive dual-drug delivery MOF hybrids paves the way to assemble of other MOF hybrids that respond to other triggering factors such as light, temperature, pH, or biomarkers. The properties and functions of such materials are expected to influence the development of sensors, new catalysts, photonic devices, and drug delivery carriers.

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Hyaluronan based Multifunctional Nano-carriers for Combination Cancer Therapy

Current Topics in Medicinal Chemistry ◽

10.2174/1568026620666200922113846 ◽

2020 ◽

Vol 20 ◽

Author(s):

Menghan Gao ◽

Hong Deng ◽

Weiqi Zhang

Keyword(s):

Cancer Therapy ◽

Combination Therapy ◽

Cancer Cells ◽

Drug Loading ◽

Tumor Therapy ◽

Drug Carriers ◽

Functional Sites ◽

Therapeutic Modalities ◽

Combination Cancer Therapy ◽

Targeting Strategy

: Hyaluronan (HA) is a natural linear polysaccharide that has excellent hydrophilicity, biocompatibility, biodegradability, and low immunogenicity, making it one of the most attractive biopolymers used for biomedical researches and applications. Due to the multiple functional sites on HA and its intrinsic affinity for CD44, a receptor highly expressed on various cancer cells, HA has been widely engineered to construct different drug-loading nanoparticles (NPs) for CD44- targeted anti-tumor therapy. When a cocktail of drugs is co-loaded in HA NP, a multifunctional nano-carriers could be obtained, which features as a highly effective and self-targeting strategy to combat the cancers with CD44 overexpression. The HA-based multidrug nano-carriers can be a combination of different drugs, various therapeutic modalities, or the integration of therapy and diagnostics (theranostics). Up to now, there are many types of HA-based multidrug nano-carriers constructed by different formulation strategies including drug co-conjugates, micelles, nano-gels and hybrid NP of HA and so on. This multidrug nano-carrier takes the full advantages of HA as NP matrix, drug carriers and targeting ligand, representing a simplified and biocompatible platform to realize the targeted and synergistic combination therapy against the cancers. In this review, recent progresses about HA-based multidrug nano-carriers for combination cancer therapy are summarized and its potential challenges for translational applications have been discussed.

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Cellular control of human multidrug resistance 1 (mdr-1) gene expression in absence and presence of gene amplification in human cancer cells.

Journal of Biological Chemistry ◽

10.1016/s0021-9258(17)32021-5 ◽

1994 ◽

Vol 269 (32) ◽

pp. 20503-20508 ◽

Cited By ~ 3

Author(s):

K. Kohno ◽

H. Tanimura ◽

S. Sato ◽

Y. Nakayama ◽

Y. Makino ◽

...

Keyword(s):

Gene Expression ◽

Multidrug Resistance ◽

Cancer Cells ◽

Gene Amplification ◽

Human Cancer ◽

Human Cancer Cells ◽

Cellular Control ◽

Mdr 1

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Quantum Dots as a Good Carriers of Unsymmetrical Bisacridines for Modulating Cellular Uptake and the Biological Response in Lung and Colon Cancer Cells

Nanomaterials ◽

10.3390/nano11020462 ◽

2021 ◽

Vol 11 (2) ◽

pp. 462 ◽

Cited By ~ 1

Author(s):

Joanna Pilch ◽

Patrycja Kowalik ◽

Piotr Bujak ◽

Anna M. Nowicka ◽

Ewa Augustin

Keyword(s):

Quantum Dots ◽

Cancer Cells ◽

Cellular Uptake ◽

Laser Scanning ◽

Biological Response ◽

Drug Carriers ◽

Confocal Laser ◽

Normal Cells ◽

H460 Cells ◽

Hct116 Cells

Nanotechnology-based drug delivery provides a promising area for improving the efficacy of cancer treatments. Therefore, we investigate the potential of using quantum dots (QDs) as drug carriers for antitumor unsymmetrical bisacridine derivatives (UAs) to cancer cells. We examine the influence of QD–UA hybrids on the cellular uptake, internalization (Confocal Laser Scanning Microscope), and the biological response (flow cytometry and light microscopy) in lung H460 and colon HCT116 cancer cells. We show the time-dependent cellular uptake of QD–UA hybrids, which were more efficiently retained inside the cells compared to UAs alone, especially in H460 cells, which could be due to multiple endocytosis pathways. In contrast, in HCT116 cells, the hybrids were taken up only by one endocytosis mechanism. Both UAs and their hybrids induced apoptosis in H460 and HCT116 cells (to a greater extent in H460). Cells which did not die underwent senescence more efficiently following QDs–UAs treatment, compared to UAs alone. Cellular senescence was not observed in HCT116 cells following treatment with both UAs and their hybrids. Importantly, QDgreen/red themselves did not provoke toxic responses in cancer or normal cells. In conclusion, QDs are good candidates for targeted UA delivery carriers to cancer cells while protecting normal cells from toxic drug activities.

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Natural and Designed Toxins for Precise Therapy: Modern Approaches in Experimental Oncology

International Journal of Molecular Sciences ◽

10.3390/ijms22094975 ◽

2021 ◽

Vol 22 (9) ◽

pp. 4975

Author(s):

Olga Shilova ◽

Elena Shramova ◽

Galina Proshkina ◽

Sergey Deyev

Keyword(s):

Cancer Cells ◽

Targeted Delivery ◽

Combined Therapy ◽

Drug Carriers ◽

Cytotoxic Action ◽

Growth And Survival ◽

Surface Receptors ◽

Nanosized Materials ◽

Natural Toxins ◽

Protein Toxins

Cancer cells frequently overexpress specific surface receptors providing tumor growth and survival which can be used for precise therapy. Targeting cancer cell receptors with protein toxins is an attractive approach widely used in contemporary experimental oncology and preclinical studies. Methods of targeted delivery of toxins to cancer cells, different drug carriers based on nanosized materials (liposomes, nanoparticles, polymers), the most promising designed light-activated toxins, as well as mechanisms of the cytotoxic action of the main natural toxins used in modern experimental oncology, are discussed in this review. The prospects of the combined therapy of tumors based on multimodal nanostructures are also discussed.

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LDH-doped electrospun short fibers enable dual drug loading and multistage release for chemotherapy of drug-resistant cancer cells

New Journal of Chemistry ◽

10.1039/d1nj02159a ◽

2021 ◽

Author(s):

Yupei Ma ◽

Du Li ◽

Yunchao Xiao ◽

Zhijun OuYang ◽

Mingwu Shen ◽

...

Keyword(s):

Multidrug Resistance ◽

Cancer Cells ◽

Cancer Chemotherapy ◽

Side Effect ◽

Drug Loading ◽

Adverse Side Effect ◽

Drug Resistant ◽

Short Fibers ◽

Dual Drug

Conventional cancer chemotherapy is facing difficulties in improving the bioavailability, overcoming the severe adverse side effect of chemotherapeutics and reversing the multidrug resistance of cancer cells. To address these challenges,...

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