Accelerated cascade melanoma therapy using enzyme-nanozyme-integrated dissolvable polymeric microneedles.

Autor: Singh P; Department of Biological Applied Engineering, Shenzhen Polytechnic, Shenzhen 518055, China., Chen Y; Shenzhen Siyomicro BIO-TECH CO., Ltd., Shenzhen 518116, China., Youden B; Department of Biology, University of Waterloo, 200 University Ave W, Waterloo, ON N2L 3G1, Canada., Oakley D; Department of Biology, Cape Breton University, 1250 Grand Lake Road, Sydney, Nova Scotia B1P 6L2, Canada., Carrier A; Department of Chemistry, Cape Breton University, 1250 Grand Lake Road, Sydney, Nova Scotia B1P 6L2, Canada., Oakes K; Department of Biology, Cape Breton University, 1250 Grand Lake Road, Sydney, Nova Scotia B1P 6L2, Canada., Servos M; Department of Biology, University of Waterloo, 200 University Ave W, Waterloo, ON N2L 3G1, Canada., Jiang R; Department of Biology, University of Waterloo, 200 University Ave W, Waterloo, ON N2L 3G1, Canada; Department of Medical Physics, Grand River Regional Cancer Centre, Kitchener, ON N2G 1G3, Canada. Electronic address: Runqing.jiang@grhosp.on.ca., Zhang X; Department of Chemistry, Cape Breton University, 1250 Grand Lake Road, Sydney, Nova Scotia B1P 6L2, Canada. Electronic address: Xu_Zhang@cbu.ca.
Jazyk: angličtina
Zdroj: International journal of pharmaceutics [Int J Pharm] 2024 Mar 05; Vol. 652, pp. 123814. Date of Electronic Publication: 2024 Jan 26.
DOI: 10.1016/j.ijpharm.2024.123814
Abstrakt: Dissolvable polymeric microneedles (DPMNs) have emerged as a powerful technology for the localized treatment of diseases, such as melanoma. Herein, we fabricated a DPMN patch containing a potent enzyme-nanozyme composite that transforms the upregulated glucose consumption of cancerous cells into lethal reactive oxygen species via a cascade reaction accelerated by endogenous chloride ions and external near-infrared (NIR) irradiation. This was accomplished by combining glucose oxidase (Gox) with a NIR-responsive chloroperoxidase-like copper sulfide (CuS) nanozyme. In contrast with subcutaneous injection, the microneedle system highly localizes the treatment, enhancing nanomedicine uptake by the tumor and reducing its systemic exposure to the kidneys and spleen. NIR irradiation further controls the potency and toxicity of the formulation by thermally disabling Gox. In a mouse melanoma model, this unique combination of photothermal, starvation, and chemodynamic therapies resulted in complete tumor eradication (99.2 ± 0.8 % reduction in tumor volume within 10 d) without producing signs of systemic toxicity. By comparison, other treatment combinations only resulted in a 42-76.5 % reduction in tumor growth. The microneedle patch design is therefore not only highly potent but also with regulated toxicity and improved safety.
Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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