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WIREs Nanomed Nanobiotechnol
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NIR light‐triggered nanomaterials‐based prodrug activation towards cancer therapy

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Abstract Nanomaterials‐based prodrug activation systems have been widely explored in cancer therapy, aiming at overcoming limited dosage formulation, systemic toxicity, and insufficient pharmacokinetic performance of parent drugs. For better delivery control, various stimuli systems, especially nanomaterials‐based ones, have come to the forefront. Among them, near‐infrared (NIR) light takes advantage of on‐demand/site‐specific regulation and non‐invasiveness. In this review, we will address the developments of nanomaterials‐based prodrug over the last decade, the activation mechanisms, and bioapplications under NIR light triggering. The advantages and limitations of NIR‐triggered prodrug activation strategies and the perspectives of the next‐generation prodrug nanomedicine will also be summarized. This article is categorized under: Therapeutic Approaches and Drug Discovery > Nanomedicine for Oncologic Disease Therapeutic Approaches and Drug Discovery > Emerging Technologies
(a) Energy transfer mechanisms of upconversion processes involved in Tm3+, Yb3+, and Er3+ doped crystals upon 980 nm laser irradiation (Reprinted with permission from Wang and Liu (2009), Copyright 2009 Royal Society of Chemistry). (b) Modification process of o‐phosphorylethanolamine‐terminated UCNPs with ONB‐FU, and release process of chemotherapeutic 5‐FU with the assistance of a 980 nm laser (Reprinted with permission from Fedoryshin, Tavares, Petryayeva, Doughan, and Krull (2014), Copyright 2014 American Chemical Society). Schematic representations of (c) release of DOX from folate‐conjugated dendrimer‐modified UCNPs (Reprinted with permission from Wong et al. (2015), Copyright 2015 Wiley‐VCH Verlag GmbH & Co. KGaA, Weinheim), (d) NIR light activation of platinum (IV) to platinum (II) and related real‐time imaging by UCNPs in the presence of long‐wavelength light (Reprinted with permission from Min, Li, Liu, Yeow, and Xing (2014), Copyright 2014 Wiley‐VCH Verlag GmbH & Co. KGaA, Weinheim), (e) a DNA strands nanopump assembly and corresponding release process under 980 nm light irradiation (Reprinted with permission from Ju et al. (2019), Copyright 2019 Wiley‐VCH Verlag GmbH & Co. KGaA, Weinheim)
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Schematic diagrams of (a) 7‐amino coumarin release from the surface of mesoporous silica upon one‐ or two‐photon NIR excitation (Reprinted with permission from Lin et al. (2010), Copyright 2010 American Chemical Society), (b) two‐photon‐activated anticancer drug (camptothecin) for cancer therapy and fluorescence imaging (Reprinted with permission from Liu et al., 2017), Copyright 2017 The Royal Society of Chemistry), and (c) two‐photon catalysis process of two prodrug molecules via 1O2 (Reprinted with permission from Lin et al. (2018), Copyright 2017 American Chemical Society)
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(a) Schematic illustration of activating combretastatin A‐4 by cleaving aminoacrylate from low‐energy‐light‐activatable prodrug (Reprinted with permission from Bio et al. (2013), Copyright 2013 American Chemical Society). (b) Structures of adamantane‐modified aza‐BODIPY and paclitaxel, as well as diblock copolymer, the self‐assembly process of the nanoparticles and combination therapy process (Reprinted with permission from Chen et al. (2019), Copyright 2019 Wiley‐VCH Verlag GmbH & Co. KGaA, Weinheim). (c) The mechanism for cleavage of olefin linkers via a [2 + 2] cycloaddition reaction with 1O2 (Reprinted with permission from Cadahía et al. (2019), Copyright 2019 Royal Society of Chemistry). (d) Structures of PPC–TK–DOX and 1,2‐dioleoyl‐sn‐glycero‐3‐phosphocholine, and corresponding ROS activation mechanism (Reprinted with permission from Zhou et al. (2017), Copyright 2017 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
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Schematic illustrations of (a) NIR light‐triggered formation and breaking of the ester bond between the carboxyl group of yolk‐shell nanocomposite containing Ag element and hydroxyl group of DOX (Reprinted with permission from Chen et al. (2013), Copyright 2012 Elsevier Ltd.), (b) DNA agonist released and regulated cell behavior via remote activation (Reprinted with permission from Wang, Zhang, et al. (2019), Copyright 2019 American Chemical Society) and (c) GNs with different structures influence siRNA delivery and its biological activity. (d) Loading and (e) releasing efficiencies of siRNA in the groups of HGNC, GNR, and HGNS. (Reprinted with permission from Morgan, Wupperfeld, Morales, and Reich (2019), Copyright 2019 American Chemical Society)
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Schematic illustration of NLNPs activation towards cancer therapy and the corresponding mechanisms
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(a) Schematic illustration of remote activation of DSP‐mediated gene expression under 808 nm laser irradiation. (b) in vitro and (c) in vivo quantification of changes in bioluminescence intensities with and without laser irradiation at 808 nm (Reprinted with permission from Lyu et al. (2017), Copyright 2017 Wiley‐VCH Verlag GmbH & Co. KGaA, Weinheim). (d) Hematoxylin & eosin (upper) and TUNEL (lower) staining images and (e) relative tumor volume curves of tumors collected from mice in various groups after different treatments. Scale bars are 50 μm. *p < .05, **p < .01, ***p < .001 (Reprinted with permission from Wang, He, et al. (2019), Copyright 2019 American Chemical Society)
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(a) Degradation behaviors of liposome–gold nanocomplex in simulated lysosomal fluid observed by a transmission electron microscope. Scale bars are 100 nm (Reprinted with permission from Zhang, Han, et al. (2019), Copyright 2019 The Authors). (b) Schematic diagram of [email protected]‐mediated chemo‐photothermal therapy. (c) Release profiles of the exogenous enzyme from [email protected] with or without 808 nm laser irradiation (2 W cm−2, 3 min). (d) Western blotting analysis of different protein expressions in 4T1 cells after different treatments (Reprinted with permission from Cheng et al. (2019), Copyright 2019 Wiley‐VCH Verlag GmbH & Co. KGaA, Weinheim). (e) Schematic representation of NIR light‐triggered photodynamic therapy and chemo‐cascade therapy. (f) Relative viabilities of 4T1 cells with different treatments. *p < .05 (Reprinted with permission from Zhao, Wu, Hu, and Xing (2017), Copyright 2017 Elsevier Ltd.)
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Therapeutic Approaches and Drug Discovery > Emerging Technologies
Therapeutic Approaches and Drug Discovery > Nanomedicine for Oncologic Disease

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