Redox-Responsive Comparison of Diselenide and Disulfide Core-Cross-Linked Micelles for Drug Delivery Application

Area of Science:

• Materials Science
• Polymer Chemistry
• Nanotechnology

Background:

• Development of responsive drug delivery systems is crucial for targeted cancer therapy.
• Polymeric micelles offer a promising platform for encapsulating hydrophobic drugs.
• Redox-sensitive linkers enable controlled drug release in specific biological environments.

Purpose of the Study:

• To synthesize and compare the redox sensitivity of diselenide (Se-Se) and disulfide (S-S) core-cross-linked (CCL) micelles.
• To evaluate the drug release kinetics and in vitro cytotoxicity of these novel micellar systems.
• To assess the potential of Se-Se CCL micelles as superior drug carriers compared to S-S CCL micelles.

Main Methods:

• Synthesis of poly(ethylene oxide)-b-poly(furfuryl methacrylate) (PEO-b-PFMA) copolymers using single electron transfer-living radical polymerization.
• Formation of PEO-b-PFMA micelles and subsequent cross-linking with maleimide derivatives to form S-S and Se-Se bonds via Diels-Alder reaction.
• Investigation of redox-responsive de-cross-linking using glutathione (GSH) and hydrogen peroxide (H2O2), dynamic light scattering (DLS) for size analysis, in vitro drug release studies, and cytotoxicity assays.

Main Results:

• Both S-S and Se-Se CCL micelles maintained structural stability under physiological conditions but underwent de-cross-linking in the presence of GSH.
• Se-Se bonds showed greater sensitivity to H2O2-induced de-cross-linking compared to S-S bonds.
• Dynamic light scattering studies indicated more significant size and PDI variations in Se-Se micelles in response to redox changes.
• In vitro studies demonstrated pH-dependent drug release, with higher release rates at pH 5.0 (tumor environment).
• DOX-loaded S-S/Se-Se CCL micelles exhibited potent cytotoxicity against BT-20 cancer cells, with no toxicity observed in HEK-293 normal cells.

Conclusions:

• The synthesized Se-Se CCL micelles exhibit superior redox sensitivity compared to S-S CCL micelles.
• These Se-Se micelles are promising candidates for enhanced, targeted drug delivery systems due to their responsiveness and efficacy.
• The PEO-b-PFMA based Se-Se CCL micelles offer a safe and effective platform for delivering anti-cancer drugs like doxorubicin.