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WIREs Nanomed Nanobiotechnol
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Insight into the efficiency of oxygen introduced photodynamic therapy (PDT) and deep PDT against cancers with various assembled nanocarriers

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Abstract Photodynamic therapy (PDT) has been used in the treatment of cancers and other benign diseases for several years in clinic. However, the hypoxia of tumors and the penetration limitation of excitation light to tissues can dramatically reduce the efficacy of PDT to cancers. To overcome these drawbacks, various assembled nanocarriers such as nanoparticles, nanocapsules, nanocrystals, and so on were introduced. The assembled nanocarriers have the ability of loading photosensitizers, delivering O2 into tumors, generating O2 in situ in tumors, as well as turning near‐infrared (NIR) light, X‐rays, and chemical energy into ultraviolet or visible light. Therefore, it is easy for the nanocarriers to improve the hypoxia microenvironment or increase the treatment depth of cancers, which will improve the efficiency of PDT to some degree. In recent years, a number of investigations were focused on these subjects. We will summarize the advances of nanocarriers in PDT, especially in O2 introduction PDT and deep PDT. The perspectives, challenges, and potential in translation of PDT will also be discussed. This article is categorized under: Therapeutic Approaches and Drug Discovery > Emerging Technologies Biology‐Inspired Nanomaterials > Lipid‐Based Structures Therapeutic Approaches and Drug Discovery > Nanomedicine for Oncologic Disease
Schematic illustration of mechanisms of type I and type II PDT
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I. (a) Schematic illustration of BL induced PDT. (b) Luminescence spectra of luminol with different amount of OPV. (c) Tumor volume changes after BL induced PDT. (Reprinted with permission from Yuan et al. (). Copyright 2012, American Chemical Society) II. (a) Formation of BL microcapsules and PDT process. (b) Persistent BL time of the microcapsules. (c) Curve a: BL spectrum of microcapsules; curve b: UV/Vis spectrum of RB; curve c: BL spectrum with the addition of RB; curve d: BL spectrum with the addition of buffer solution. (Reprinted with permission from Zhao et al. (). Copyright 2013, WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim) III. Chemical reaction in BL and BRET induced PDT process. (b) BL spectra of BLS and upconverted emission of CDs (insets). (Reprinted with permission from Yang et al. (). Copyright 2018, Springer Science Business Media, LLC)
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I. (a) Schematic illustration of RB loaded mesoporous LaF3:Tb used in X‐ray induced PDT. (b) Fluorescence intensity changes of mesoporous LaF3:Tb loaded with different amount of RB. (Reprinted with permission from Tang, Hu, Elmenoufy, and Yang (). Copyright 2015, American Chemical Society) II. (a) Schematic illustration of the formation of ZnPcS4 loaded PLNP and X‐ray mediated PDT. (b) Tumor volume changes after treatment. (Reprinted with permission from Song et al. (). Copyright 2018 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
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I. (a) Schematic illustration of 980 nm light induced PDT by upconversion luminescence. (b) TEM images of UCNPs. (c) Luminescent intensity of Ce6 loaded UCNPs at different concentrations. (Reprinted with permission from Wang, Tao, Cheng, and Liu (). Copyright 2011, Elsevier) II. (a) Structure of ZnPc and MC540 loaded UCNPs coated by folic and PEG modified mesoporous silica. (b) The fluorescence spectrum of UCNPs excited by 980 nm laser and absorption spectra of ZnPc and MC540. (c) Tumor volume changes after treatment. (Reprinted with permission from Idris et al. (). Copyright 2012, Nature Publishing Group) III a) The formation of O2/Pt(II) self‐generating nanostructures. b) The formation of ROS in hypoxia environment under 980 nm irradiation. c) The fluorescence imaging of nanostructures at different time points after injection. (Reprinted with permission from Xu et al. (). Copyright 2018, Nature Publishing Group)
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I. Schematic illustration of artificial red blood cells as PS carriers for PDT and ferryl‐Hb induced cytotoxicity. (Reprinted with permission from Luo et al. (). Copyright 2016, Nature Publishing Group) II. (a) Schematic illustration of the formation of mmRBCs, the accumulation of mmRBCs in tumors, and PDT process. (b) The tumors harvested 20 days after treatment. (Reprinted with permission from Liu, Liu, et al. (). Copyright 2018 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
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I. (a) Formation of FITC‐PGSN‐RB for TPE‐PDT. (b) Fluorescent spectra of FITC‐PGSN, FITC‐PGSN‐RB, and RB irradiated by two‐photon laser. (Reprinted with permission from Liu et al. (). Copyright 2016, WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim) II. Microcapsules fabricated with different assembly sequences (a) and the corresponding lifetime decay curves (b). (Reprinted with permission from Yang, Liu, Han, Sun, and Li (). Copyright 2016, WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim) III. The components of BP@RB‐Hb nanostructures and the FRET process. (Reprinted with permission from Cao, Wang, et al. (). Copyright 2018, WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim) IV. The constituents of AIE‐PS@liposomes and TPE‐PDT process in tumors. (Reprinted with permission from Yang et al. (). Copyright 2019, American Chemical Society)
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I. (a) Schematic illustration of the formulation of lipid‐HB‐gold nanocages and the TPE. (b) TEM images of lipid‐HB‐gold nanocages. (c) Cytotoxicity of the lipid‐HB‐gold nanocages to cancer cells. (Reprinted with permission from Gao et al. (). Copyright 2012, American Chemical Society) II. (a) The formation process of HB loaded gold nanorods based nanocomplex with high tumor selectivity for both PDT and PTT. (b) TEM images of AuNR@MSN. (c) Tumor volume after irradiation. (Reprinted with permission from Du et al. (). Copyright 2015 Royal Society of Chemistry)
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Schematic illustration of preparation of lipid‐polymer bilaminar oxygen nanobubbles conjugated with Ce6 and the PDT process. (Reprinted with permission from Song, Hu, et al. (). Copyright 2016, American Chemical Society)
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I. (a) Schematic illustration of the core‐shell structures internalization by cancer cells, H2O2 decomposition, and the PDT process. (b) Formation of 1O2 in the absence (a) and presence (B) of H2O2. (c) Viability of cells incubated with (i) control; (ii) bare CaCO3; (iii) composites without RB; (iv) composites in the dark; (v) RB solution; (vi) composites with irradiation. (Reprinted with permission from Zhao, Fei, Du, et al. (). Copyright 2014 Royal Society of Chemistry) II. (a) Schematic illustration of light‐triggered in situ formation of PS and catalase entrapped hydrogel in tumor bearing mice. (b) The growth curves of reinoculated tumors 40 days after the elimination of the first tumors by (1) control; (2) surgery removal; (3) multiple rounds of Gel‐PDT with RPNPs. (Reprinted with permission from Meng et al. (). Copyright 2019 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
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(a) Structure of the nanodroplets. (b) The accumulation of nanodroplets in tumors‐bearing mice. (c) Volume changes of tumors. (Reprinted with permission from Cheng et al. (). Copyright 2015, Nature Publishing Group)
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I. (a) Schematic illustration of PCN‐224‐Pt preparation and PDT process in the cell. (b) The formation of 1O2 in hypoxia environment. (c) Tumor volume after treatment. (Reprinted with permission from Zhang et al. (). Copyright 2018, American Chemical Society) II. (a) Schematic illustration of the structure of MFMSNs and enhanced PDT in tumor cells. (b) Repetitive decompositions of H2O2 by MFMSNs. (c) T2*‐weighted magnetic resonance images of a mouse after injection of MFMSNs. (Reprinted with permission from Kim et al. (). Copyright 2017, American Chemical Society)
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Therapeutic Approaches and Drug Discovery > Nanomedicine for Oncologic Disease
Therapeutic Approaches and Drug Discovery > Emerging Technologies
Biology-Inspired Nanomaterials > Lipid-Based Structures

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