Premium
Strengthened Tumor Photodynamic Therapy Based on a Visible Nanoscale Covalent Organic Polymer Engineered by Microwave Assisted Synthesis
Author(s) -
Lu Yao,
Song Ge,
He Bing,
Zhang Hua,
Wang Xueqing,
Zhou Demin,
Dai Wenbing,
Zhang Qiang
Publication year - 2020
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.202004834
Subject(s) - photodynamic therapy , materials science , in vivo , covalent bond , porphyrin , apoptosis , photothermal therapy , cancer research , nanotechnology , tumor microenvironment , biophysics , tumor cells , chemistry , photochemistry , biochemistry , biology , organic chemistry , microbiology and biotechnology
Covalent organic polymers (COPs) possess fascinating features including large surface area, tunable pore size, good stability, and biodegradability. As advanced functional materials, both their synthesis and potential use must be further explored. In an effort to facilitate enhanced photodynamic therapy of cancer, here a porphyrin‐containing nanoscale COPs (nCOP) via a facile microwave synthesis method, followed by the loading of a thioredoxin‐1 inhibitor PX‐12, is fabricated. The obtained nCOP‐PX‐12 is visible in vitro and in vivo due to the existence of meso ‐tetrakis(4‐aminophenyl) porphyrin (TAPP). With the acid‐cleavable imine group, it demonstrates pH‐responsive drug release. Additionally, the released TAPP achieves mitochondria targeting which can induce mitochondrial‐dependent tumor cell apoptosis with laser irradiation. The combination therapy can induce immunogenic cell death and APCs activation, while PX‐12 is found to remodel the tumor hypoxic microenvironment via blocking the downstream signaling pathways of thioredoxin‐1. The nanosystem also exhibits excellent tumor accumulation and biosafety. After a single intratumoral dose of nCOP‐PX‐12 with relatively low density of laser, 98.5% primary cancer, 65.3% untreated distant tumors and 83.2% lung metastasis are inhibited. Overall, this study improves the synthesis of multifunctional nCOP and proposes a powerful photodynamic therapy with high specificity to overcome the resistance of hypoxic tumors.