A promising strategy for synergistic cancer therapy by integrating a photosensitizer into a hypoxia-activated prodrug.
Eur J Med Chem
; 243: 114749, 2022 Dec 05.
Article
em En
| MEDLINE
| ID: mdl-36115207
ABSTRACT
Herein, we fabricate a multifunctional molecular prodrug BAC where the chemotherapeutical agent camptothecin (CPT) is linked with a boron dipyrromethene (BODIPY)-based photosensitizer by an azobenzene chain which is sensitive to over-expressed azoreductase in hypoxic tumor cells. This prodrug was further loaded into biodegradable monomethoxy poly(ethylene glycol)-b-poly(caprolactone) (mPEG-b-PCL) to improve its solubility and tumor accumulation. The formed BAC nanoparticles (BAC NPs) can destroy aerobic tumor cells with relatively short distance from blood vessels by photodynamic therapy (PDT) under illumination. The PDT action inevitably leads to consumption of O2, and subsequently acute hypoxia which can induce cleavage of azobenzene linkage to boost release of CPT killing the other hypoxic interior tumor cells survived from PDT. Both in vitro and in vivo studies have verified that BAC NPs possess remarkable antitumor activity by a synergistic action of PDT and chemotherapy.
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Base de dados:
MEDLINE
Assunto principal:
Fotoquimioterapia
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Pró-Fármacos
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Nanopartículas
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Neoplasias
Idioma:
En
Ano de publicação:
2022
Tipo de documento:
Article