Intercellular pH-responsive histidine modified dextran-g-cholesterol micelle for anticancer drug delivery

Area of Science:

• Biomaterials Science
• Nanotechnology
• Cancer Therapeutics

Background:

• Developing pH-sensitive drug delivery systems is crucial for targeted cancer therapy.
• Acidic environments within tumor endosomes and lysosomes present an opportunity for controlled drug release.
• Histidine-modified dextran-g-cholesterol (HDC) micelles offer potential for pH-responsive drug delivery.

Purpose of the Study:

• To prepare and characterize pH-sensitive micelles based on histidine modified dextran-g-cholesterol (HDC).
• To evaluate the doxorubicin (DOX) loading capacity and release profile of HDC micelles under acidic conditions.
• To assess the in vitro anticancer efficacy of DOX-loaded HDC micelles in MCF-7 cells.

Main Methods:

• Synthesis and characterization of histidine modified dextran-g-cholesterol (HDC) micelles.
• Loading of doxorubicin (DOX) into HDC micelles via hydrophobic interactions.
• In vitro drug release studies at different pH values (acidic vs. neutral).
• Cellular uptake and cytotoxicity assays using MCF-7 cancer cells.

Main Results:

• HDC micelles demonstrated excellent pH-responsive behavior in acidic aqueous solutions (pH<6).
• DOX was effectively loaded into HDC micelles, with accelerated release observed in acidic conditions mimicking endosomal/lysosomal compartments.
• Enhanced intracellular DOX release and higher cellular proliferation inhibition were observed in MCF-7 cells treated with DOX-loaded pH-sensitive micelles compared to pH-insensitive micelles.

Conclusions:

• HDC micelles serve as an efficient pH-sensitive platform for loading and delivering doxorubicin (DOX).
• The accelerated drug release in acidic tumor microenvironments enhances intracellular drug concentration.
• These pH-sensitive micelles show improved in vitro anticancer activity, offering a promising strategy for targeted cancer therapy.