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Designer Anticancer Nanoprodrugs with Self‐Toxification Activity Realized by Acid‐triggered Biodegradation and In Situ Fragment Complexation
Author(s) -
Yang Yannan,
Zhang Min,
Yang Yang,
Cheng Dan,
Yu Chengzhong
Publication year - 2021
Publication title -
angewandte chemie
Language(s) - English
Resource type - Journals
eISSN - 1521-3757
pISSN - 0044-8249
DOI - 10.1002/ange.202102704
Subject(s) - in situ , chemistry , conjugate , prodrug , degradation (telecommunications) , intracellular , biophysics , cancer cell , combinatorial chemistry , biochemistry , organic chemistry , cancer , medicine , mathematical analysis , telecommunications , mathematics , computer science , biology
Prodrugs that allow in situ chemical conversion of less toxic precursors into active drugs in response to certain stimuli are promising anticancer candidates. Herein, we present a novel design of nanoprodrugs with a “degradation‐mediated self‐toxification” strategy, which realizes intracellular synthesis of anticancer agents using the nanoparticles’ own degradation fragments as the precursors. To fulfill this concept, a metal complexing dicyclohexylphosphine (DCP) organosilane is carefully screened out from various ligands to conjugate onto Pd(OH) 2 nanodots confined hollow silica nanospheres (PD‐HSN). This constructed nanoprodrug shows acid‐triggered degradation in lysosomes and neutralizes protons to induce lysosomes rupturing, generating predesigned less toxic fragments (Pd 2+ and DCP‐silicates) that complex into DCP/Pd complex in situ for inducing DNA damage, leading to enhanced anticancer activity against various cancer cell lines as well as in a xenograft tumour model.