Leveraging Cholesterol-Functionalized Cyclodextrin Nanosponges for Enhanced Drug Delivery in Cancer Cells.

Area of Science:

• Nanotechnology for drug delivery
• Cancer therapeutics
• Biocompatible materials

Background:

• Cholesterol enhances biocompatibility and bioavailability in drug delivery systems for cancer treatment.
• Resveratrol, a natural compound, has anticancer potential but suffers from low solubility and bioavailability, limiting its clinical use.

Purpose of the Study:

• To design and evaluate cholesterol-functionalized cyclodextrin nanosponges (Chol-NSs) for optimized resveratrol encapsulation and delivery.
• To investigate the impact of tunable cholesterol content on resveratrol delivery and efficacy in breast cancer cells.

Main Methods:

• Synthesis of free carbonyl diimidazole (CDI) nanosponges (NSs) and cholesterol-functionalized Chol-NSs with varying cholesterol content.
• Assessment of drug loading and encapsulation efficiency for resveratrol.
• In vitro evaluation of cellular uptake, cytotoxicity against breast cancer cells, and safety profiles on fibroblast and cancer cell lines.

Main Results:

• Both CDI-NSs and Chol-NSs exhibited high drug loading and encapsulation efficiency for resveratrol.
• Cholesterol incorporation significantly enhanced nanocarrier cellular uptake and potentiated resveratrol's cytotoxic effects on breast cancer cells.
• All formulations, including Chol-NSs with varying cholesterol percentages, demonstrated a safe profile against both normal fibroblast and breast cancer cell lines.

Conclusions:

• Cholesterol-functionalized nanosponges are a promising platform for improving the delivery of natural compounds like resveratrol.
• This approach enhances the efficacy and safety of resveratrol-based cancer therapy.
• Tunable cholesterol content in nanosponges allows for optimization of drug delivery systems.