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A Traceable, Sequential Multistage‐Targeting Nanoparticles Combining Chemo/Chemodynamic Therapy for Enhancing Antitumor Efficacy
Author(s) -
Wang Ning,
Liu Chenyu,
Yao Weihe,
Zhou Hengjun,
Yu Simiao,
Chen Hailiang,
Qiao Weihong
Publication year - 2021
Publication title -
advanced functional materials
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.069
H-Index - 322
eISSN - 1616-3028
pISSN - 1616-301X
DOI - 10.1002/adfm.202101432
Subject(s) - prodrug , reactive oxygen species , glutathione , peg ratio , cancer research , cancer cell , biophysics , mitochondrion , materials science , angiogenesis , tumor microenvironment , pharmacology , chemistry , biochemistry , cancer , biology , tumor cells , medicine , enzyme , finance , economics
Although chemodynamic therapy (CDT) can effectively inhibit tumor growth and metastasis, it is challenging to eliminate tumors. Generally, CDT needs to combine with extra therapeutic modes for enhancing antitumor efficacy. Here, novel nanoparticles (BDTLAG NPs) are constructed via self‐assembly of cancer cell targeting prodrug (Bio‐PEG 2K ‐S‐S‐CPT), organic CDT agents (TPP‐PEG 2K ‐LND, TPP‐PEG 2K ‐TOS), pH‐responsive prodrug (PEG 2K ‐NH‐N‐DOX), T1‐enhanced magnetic resonance imaging contrast agents (Gd‐DTPA‐N16‐16), and anti‐angiogenic drug combrestatinA4 (CA4), realizing chemo(CT)‐chemodynamic combination therapy. The mechanism of BDTLAG NPs for enhancing antitumor efficacy involves: (i) BDTLAG NPs is accumulated in the tumor tissue by passive targeting; (ii) CA4 is released and specifically destroys angiogenesis, and the remaining BDTLG NPs enter the tumor cell via active targeting; (iii) the acid/glutathione (GSH)‐responsive prodrug release and GSH depletion; (iv) TPP‐PEG 2K ‐LND and TPP‐PEG 2K ‐TOS are accumulated in the tumor cell mitochondria due to mitochondria‐targeting, and is accompanied by endogenous reactive oxygen species bursts. This current strategy of single NPs that integrates spatiotemporally CT, CDT, GSH depletion, and MR imaging functions reflects the “all in one” concept, which provides a new opportunity for enhancing antitumor efficacy.