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WIREs Nanomed Nanobiotechnol
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Nanomedicines for combating multidrug resistance of cancer

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Abstract Chemotherapy typically involves the use of specific chemodrugs to inhibit the proliferation of cancer cells, but the frequent emergence of a variety of multidrug‐resistant cancer cells poses a tremendous threat to our combat against cancer. The fundamental causes of multidrug resistance (MDR) have been studied for decades, and can be generally classified into two types: one is associated with the activation of diverse drug efflux pumps, which are responsible for translocating intracellular drug molecules out of the cells; the other is linked with some non‐efflux pump‐related mechanisms, such as antiapoptotic defense, enhanced DNA repair ability, and powerful antioxidant systems. To overcome MDR, intense efforts have been made to develop synergistic therapeutic strategies by introducing MDR inhibitors or combining chemotherapy with other therapeutic modalities, such as phototherapy, gene therapy, and gas therapy, in the hope that the drug‐resistant cells can be sensitized toward chemotherapeutics. In particular, nanotechnology‐based drug delivery platforms have shown the potential to integrate multiple therapeutic agents into one system. In this review, the focus was on the recent development of nanostrategies aiming to enhance the efficiency of chemotherapy and overcome the MDR of cancer in a synergistic manner. Different combinatorial strategies are introduced in detail and the advantages as well as underlying mechanisms of why these strategies can counteract MDR are discussed. This review is expected to shed new light on the design of advanced nanomedicines from the angle of materials and to deepen our understanding of MDR for the development of more effective anticancer strategies. This article is categorized under: Nanotechnology Approaches to Biology > Nanoscale Systems in Biology Therapeutic Approaches and Drug Discovery > Nanomedicine for Oncologic Disease
Scheme illustrating the mechanisms of MDR
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(a) Scheme illustrating the preparation of GOx&[email protected] and its working mechanism to combat multidrug‐resistant tumors. Reprinted with permission from Y. Chen, Yao, et al. (2019d). Copyright 2019 American Chemical Society. (b) Schematic illustration of the fabrication of DDTF nanocomplexes and their anticancer mechanism by inducing apoptosis/ferroptosis in cancer cells. (c) Confocal images indicating the intranuclear DOX delivery by DDTF in MCF‐7/ADR cells. (d) Confocal images indicating the expression of P‐gp in MCF‐7/ADR cells after various treatments. (b–d) Reprinted with permission from Guo et al. (2019). Copyright 2019 American Chemical Society
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(a) Scheme showing the fabrication and NIR light‐triggered CO delivery of PPPPB–CO–Dox for MDR reversal. Reprinted with permission from Li, Dang, et al. (2019b). Copyright 2019 American Chemical Society. (b) Schematic illustration of the fabrication of MON‐[email protected]‐DOX and its mechanisms of redox‐responsive DOX/SO2 release and combination therapy. Reprinted with permission from X. Yao, Ma, et al. (2020b). Copyright 2020 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim
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(a) Scheme illustrating the action mechanism of NO for overcoming MDR. Reprinted with permission from Kim et al. (2017). Copyright 2017 Elsevier Ltd. (b) Schematic diagram of the synthetic route of [email protected] and [email protected] and their synergistic action for combating multidrug‐resistant cancer. Reprinted with permission from Wei et al. (2019). Copyright 2019 Elsevier Ltd. (c) Scheme illustrating the anti‐MDR mechanism of [email protected]3‐BNN6/DOX. (d) Confocal imaging and flow cytometry results of MCF‐7/ADR cells subjected to different treatments as indicated. The cells were irradiated by a 980 nm laser for 10 min in the [email protected]‐BNN6/DOX + NIR group. The cell nuclei were stained with Hoechst 33342. (c and d): Reprinted with permission from S. Li, Song, et al. (2020b). Copyright 2020 American Chemical Society
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(a) Scheme illustrating the action mechanism of PpIX/Dox liposomes in killing the drug‐sensitive and drug‐resistant cancer cells with the help of PDT. (b) Confocal fluorescence images of PpIX/Dox liposome‐treated MCF‐7/ADR cells costained with Hoechst 33342 after laser irradiation and the fluorescence intensity profiles of the two marked lines i and ii. (c) Cell viabilities of MCF‐7/ADR cells treated with PpIX/Dox liposomes after laser irradiation (635 nm, 5 mW/cm2, 3 min). (d) Apoptosis/necrosis assay results of PpIX/Dox liposome‐treated MCF‐7/ADR cells after laser irradiation (635 nm, 5 mW/cm2, 3 min). (a–c): Reprinted with permission from Y. X. Zhu, Jia, Duan, et al. (2020b). Copyright 2020 American Chemical Society
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(a) Scheme showing the structure of the amphiphilic triblock copolymer PolyPt/Ru and its degradation, 1O2 generation, and drug release triggered by red light irradiation. Reprinted with permission from Zeng et al. (2020). Copyright 2020 Elsevier Ltd. (b) Scheme illustrating the preparation and structure of PCF‐MB, and its conversion to PCF‐NPs by UTMD. (c) Schematic illustration displaying the chemo‐photodynamic therapy mediated by PCF‐MB with the assistance of the UTMD technique. (b and c): Reprinted with permission from Chen et al. (2018). Copyright 2018 American Chemical Society
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(a) Schematic illustration of the synthetic route of M‐[email protected]‐PDA‐PEG‐FA‐D and its application in photothermal/chemo/gene combination therapy. Reprinted with permission from Cheng et al. (2017). Copyright 2017 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim. (b) Scheme displaying the fabrication of the copolymer‐based nanovector D/siR‐CP and its pH‐responsive release of DOX and siRNA. Reprinted with permission from Sun et al. (2018). Copyright 2018 American Chemical Society. (c) MDR reversal, cytoskeleton damage, and apoptosis induction of Se/[email protected]‐101‐(P+V)siRNA NPs in MCF‐7/T cancer cells. Confocal imaging results of actin (d) and microtubule (e) damage in MCF‐7/T cells after different treatments as indicated. (c–e): Reprinted with permission from Chen et al. (2017). Copyright 2017 American Chemical Society
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Therapeutic Approaches and Drug Discovery > Nanomedicine for Oncologic Disease
Nanotechnology Approaches to Biology > Nanoscale Systems in Biology

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