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WIREs Nanomed Nanobiotechnol
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Physical‐, chemical‐, and biological‐responsive nanomedicine for cancer therapy

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Abstract Cancer therapy is unsatisfactory as it typically has serious side effects, because normal cells in healthy organs are destroyed along with the tumor. Thus, researchers have tried to develop effective therapies with minimal side effects. One such method is to use nanotechnology to carry the drugs or therapeutic agents to the tumor region by secure encapsulation without leakage. Once the nanomedicine enters the target tumor site, it can release therapeutic agents in an effective manner. Accordingly, various nanomedicines have been developed to enhance the efficiency of cancer therapy and minimize the systematic toxicity. Here, we provide an overview and discuss the different types of responsive nanomedicines including physically, chemically, biologically, dual, and multi‐responsive nanomedicines, for the in situ release of cargos in recent years. We propose critical considerations that must be considered for the design of excellent stimuli‐nanomedicine. Furthermore, the possible directions for the development of successful stimuli‐responsive (smart) nanomedicine are highlighted. With the development of responsive nanomedicines, precise and personalized nanomedicine will be realized with great promise in the future. This article is categorized under: Therapeutic Approaches and Drug Discovery > Nanomedicine for Oncologic Disease Nanotechnology Approaches to Biology > Nanoscale Systems in Biology
Different types of responsive nanomedicine in tumor therapy
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(a) Schematic design of the IDD coated HN (IDDHN). (b) Schematic illustration of the synergistic effects for deep tumor penetration and therapy effects. (Reprinted with permission from C. Hu, Cun, et al. (). Copyright 2018 Elsevier)
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Schematic illustration of a cascade amplification release nanoparticle (CARN) and its sequential release process. (a) Chemical structure of Lapa, the prodrug BDOX, and the poly(ethylene glycol)‐poly[2‐(methylacryloyl)ethylnicotinate] (PEG‐PMAN) carrier and their cascade drug release mechanism. (b) After intravenous injection, CARNs are accumulated in tumor tissues because of the enhanced permeation and retention (EPR) effect and internalized by cancer cells. Lapa is first discharged from the nanoparticle and generates abundant ROS via the catalysis of the overexpressed NQO1 enzyme, which feeds back to the nanoparticle to transform BDOX into DOX and promotes substantially accelerated drug release. Meanwhile, the generated ROS can also inhibit the function of P‐gp, block the efflux of DOX, facilitate the nuclear transportation of DOX, and finally induce apoptosis. In normal cells, the intracellular ROS level is barely affected by Lapa due to their low NQO1 expression, which keeps BDOX inert and innocuous in the nanoparticle. (Reprinted with permission from M. Ye et al. (). Copyright 2017 Wiley)
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(a) Schematic illustration of the hybrid polymeric system consisting of Ce6, DOX, and MnO2 co‐loaded nanoparticles (CDM NPs) prepared by a double emulsion solvent evaporation method. (b) Schematic illustration of tumor‐targeting CDM NPs for combined O2‐generating chemo‐photodynamic cancer therapy and trimodal fluorescence (FI), photoacoustic (PA) and magnetic resonance imaging (MRI). (Reprinted with permission from D. Hu, Chen, et al. (). Copyright 2018 Ivyspring International Publisher)
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Graphical illustration of the sequential events of the nanoparticle‐loaded nanoparticle carriers comprising the prepared LPMSN and drug‐loaded DNA‐gold nanoparticles (AuNPs): Tumor‐specific accumulation, deep penetration, cellular internalization, and intracellular drug release. (Reprinted with permission from J. Kim, Jo, et al. (). Copyright 2018 Wiley)
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Schematic diagram of the release of nanodroplets complex triggered by low‐intensity focused ultrasound radiation at different stages. (Reprinted with permission from Y. Cao et al. (). Copyright 2018 Ivyspring International Publisher)
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Design of perfluorohexane (PFH)‐loaded magnetic hollow iron oxide nanoparticles (HIONs) for magnetic droplet vaporization (MDV)‐based intelligent stimuli‐responsive cancer theranostics. (a) Schematic illustration of the MDV process mediated by PFH‐HIONs, including encapsulation of PFH into HIONs and subsequent vaporization of PFH induced by the alternating current magnetic field. (b) The schematic illustration of the MDV apparatus for MDV process to generate microbubbles. (c) in vivo MDV process for imaging‐guided cancer theranostics. (Reprinted with permission from Y. Zhou et al. (). Copyright 2016 Nature)
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Coordination‐precipitation process of (a) Me‐RBS and (b) NIR‐responsive release of NO. (Reprinted with permission from L. Chen et al. (). Copyright 2017 American Chemical Society)
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Nanotechnology Approaches to Biology > Nanoscale Systems in Biology
Therapeutic Approaches and Drug Discovery > Nanomedicine for Oncologic Disease

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