pH/Reduction Dual-Responsive Diselenide-Containing Mixed Cross-Linked Micelles for Folic Acid-Targeted Doxorubicin...

Area of Science:

• Biomaterials Science
• Polymer Chemistry
• Nanotechnology

Background:

• Polymeric micelles offer potential for controlled drug delivery.
• Folic acid modification enhances tumor targeting.
• pH-responsive polymers are crucial for stimuli-triggered drug release.

Purpose of the Study:

• To develop dual-responsive, self-cross-linked micelles for improved doxorubicin delivery.
• To enhance micelle stability and drug retention under physiological conditions.
• To evaluate the tumor-targeting and anticancer efficacy of the novel micelles.

Main Methods:

• Synthesis of folic acid-modified polymers (FA-P1-SA and P2-SA) with selenooctanoic acid.
• Construction of dual-responsive diselenide-containing mixed cross-linked micelles (MCLM).
• Characterization using NMR, FT-IR, Raman spectroscopy, GPC, and dissipative particle dynamics (DPD).
• In vitro drug release studies under physiological and reductive, acidic conditions.
• Cytotoxicity assays and in vivo anticancer efficacy evaluation.

Main Results:

• Successful synthesis and characterization of SA-conjugated polymers with ~70% esterification.
• MCLM demonstrated superior drug retention under physiological conditions compared to non-cross-linked micelles.
• Rapid, stimuli-triggered doxorubicin release was observed in reductive, acidic environments.
• Minimal polymer toxicity was noted post-SA modification.
• FA-containing MCLM showed enhanced tumor targeting and anticancer efficacy.

Conclusions:

• Folic acid-modified, dual-responsive, diselenide-containing mixed cross-linked micelles offer improved stability and controlled drug release.
• These micelles exhibit potential for effective tumor-targeted drug delivery and cancer therapy.
• The self-cross-linking strategy enhances micelle performance in drug delivery applications.