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Self-supplying Cu 2+ and H 2 O 2 synergistically enhancing disulfiram-mediated melanoma chemotherapy.
- Source :
-
RSC advances [RSC Adv] 2024 Apr 23; Vol. 14 (19), pp. 13180-13189. Date of Electronic Publication: 2024 Apr 23 (Print Publication: 2024). - Publication Year :
- 2024
-
Abstract
- Disulfiram (DSF) can target and kill cancer cells by disrupting cellular degradation of extruded proteins and has therefore received particular attention for its tumor chemotherapeutic potential. However, the uncontrollable Cu <superscript>2+</superscript> /DSF ratio reduces the efficacy of DSF-mediated chemotherapy. Herein, self-supplying Cu <superscript>2+</superscript> and oxidative stress synergistically enhanced DSF-mediated chemotherapy is proposed for melanoma-based on PVP-coated CuO <subscript>2</subscript> nanodots (CPNDs). Once ingested, DSF is broken down to diethyldithiocarbamate (DTC), which is delivered into a tumor via the circulation. Under the acidic tumor microenvironment, CPNDs produce sufficient Cu <superscript>2+</superscript> and H <subscript>2</subscript> O <subscript>2</subscript> . DTC readily chelates Cu <superscript>2+</superscript> ions to generate CuET, which shows antitumor efficacy. CuET-mediated chemotherapy can be enhanced by H <subscript>2</subscript> O <subscript>2</subscript> . Sufficient Cu <superscript>2+</superscript> generation can guarantee the maximum efficacy of DSF-mediated chemotherapy. Furthermore, released Cu <superscript>2+</superscript> can be reduced to Cu <superscript>+</superscript> by glutathione (GSH) and O <superscript>2-</superscript> in tumor cells, and Cu <superscript>+</superscript> can react with H <subscript>2</subscript> O <subscript>2</subscript> to generate toxic hydroxyl radicals (·OH) via a Fenton-like reaction, promoting the efficacy of CuET. Therefore, this study hypothesizes that employing CPNDs instead of Cu <superscript>2+</superscript> ions could enhance DSF-mediated melanoma chemotherapy, providing a simple but efficient strategy for achieving chemotherapeutic efficacy.<br />Competing Interests: There are no conflicts to declare.<br /> (This journal is © The Royal Society of Chemistry.)
Details
- Language :
- English
- ISSN :
- 2046-2069
- Volume :
- 14
- Issue :
- 19
- Database :
- MEDLINE
- Journal :
- RSC advances
- Publication Type :
- Academic Journal
- Accession number :
- 38655468
- Full Text :
- https://doi.org/10.1039/d4ra01075b