Biodegradable nanoemulsion-based bioorthogonal nanocatalysts for intracellular generation of anticancer therapeutics

Bioorthogonal catalysis mediated by transition metal catalysts (TMCs) provides controlled in situ activation of prodrugs through chemical reactions that do not interfere with cellular bioprocesses. The direct use of 'naked' TMCs in biological environments can have issues of solubility, dea...

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Bibliographic Details
Published in:Nanoscale 2023-08, Vol.15 (33), p.13595-1362
Main Authors: Nabawy, Ahmed, Gupta, Aarohi, Jiang, Mingdi, Hirschbiegel, Cristina-Maria, Fedeli, Stefano, Chattopadhyay, Aritra Nath, Park, Jungmi, Zhang, Xianzhi, Liu, Liang, Rotello, Vincent M
Format: Article
Language:English
Subjects:
Animals
Biocompatibility
Catalysis
Catalytic activity
Cationic polymerization
Chemical reactions
Mammals
Nanoemulsions
Palladium
Palladium - pharmacology
Prodrugs - pharmacology
Prodrugs - therapeutic use
Transition Elements
Transition metals
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Summary:Bioorthogonal catalysis mediated by transition metal catalysts (TMCs) provides controlled in situ activation of prodrugs through chemical reactions that do not interfere with cellular bioprocesses. The direct use of 'naked' TMCs in biological environments can have issues of solubility, deactivation, and toxicity. Here, we demonstrate the design and application of a biodegradable nanoemulsion-based scaffold stabilized by a cationic polymer that encapsulates a palladium-based TMC, generating bioorthogonal nanocatalyst "polyzymes". These nanocatalysts enhance the stability and catalytic activity of the TMCs while maintaining excellent mammalian cell biocompatibility. The therapeutic potential of these nanocatalysts was demonstrated through efficient activation of a non-toxic prodrug into an active chemotherapeutic drug, leading to efficient killing of cancer cells. A biodegradable nanoemulsion to encapsulate hydrophobic transition metal catalysts (TMCs) and perform intracellular bioorthogonal activation of prodrugs for anticancer therapy.
ISSN:2040-3364
2040-3372
2040-3372
DOI:10.1039/d3nr01801f