Actively Targeting Redox-Responsive Multifunctional Micelles for Synergistic Chemotherapy of Cancer

Area of Science:

• Biomaterials Science
• Nanotechnology
• Cancer Therapeutics

Background:

• Stimuli-responsive polymeric micelles are promising for drug delivery, enhancing efficacy and reducing side effects.
• Targeted delivery systems are crucial for improving cancer treatment outcomes.

Purpose of the Study:

• To synthesize and characterize a novel digoxin-modified, redox-responsive, disulfide-linked poly(ethylene glycol-b-poly(lactic-co-glycolic acid)) copolymer (Bi(Dig-PEG-PLGA)-S2).
• To evaluate its potential as a multifunctional drug delivery vehicle for targeted and controlled release of doxorubicin (DOX) in cancer cells.

Main Methods:

• Self-assembly of Bi(Dig-PEG-PLGA)-S2 into spherical micelles.
• Characterization of micelle size, zeta potential, serum, and colloidal stability.
• Assessment of drug loading capacity (DLC) and encapsulation efficiency (EE).
• In vitro evaluation of doxorubicin (DOX) release under redox conditions (GSH and H2O2).
• In vitro studies in HeLa cell lines to assess intracellular accumulation and apoptotic effects.

Main Results:

• Bi(Dig-PEG-PLGA)-S2 formed uniform spherical micelles (58.36 ± 0.78 nm) with good stability.
• High drug loading capacity (6.26%) and encapsulation efficiency (83.23%) were achieved.
• Redox-responsive DOX release was observed, with significant release in the presence of GSH and H2O2.
• DOX@Bi(Dig-PEG-PLGA)-S2 demonstrated enhanced intracellular accumulation and apoptotic effects in HeLa cells.

Conclusions:

• The synthesized Bi(Dig-PEG-PLGA)-S2 micelles are effective for targeted and controlled doxorubicin delivery.
• Digoxin moiety enhances cellular uptake and chemosensitization, improving anti-cancer effects.
• These findings highlight the potential of Bi(Dig-PEG-PLGA)-S2 as a multifunctional nanocarrier for cancer therapy.