Journal
ADVANCED FUNCTIONAL MATERIALS
Volume 30, Issue 45, Pages -Publisher
WILEY-V C H VERLAG GMBH
DOI: 10.1002/adfm.202004834
Keywords
hypoxic tumors; microwave synthesis; nanoscale organic polymers; photodynamic therapy; thioredoxin-1 inhibitors
Categories
Funding
- National Key R&D Program of China [2017YFA0205600]
- National Science Foundation of China [81690264, 81821004, 31671017, 81703441, 81872809]
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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 ofmeso-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.
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