Self-assembled polypeptide nanoparticles for intracellular irinotecan delivery.

Area of Science:

• Biomaterials Science
• Nanotechnology
• Drug Delivery

Background:

• Development of novel nanocarriers for targeted drug delivery is crucial for improving therapeutic efficacy and reducing side effects.
• Polymersomes offer a versatile platform for encapsulating various therapeutic agents due to their tunable properties and biocompatibility.

Purpose of the Study:

• To synthesize and characterize poly(l-lysine)-b-poly(l-leucine) (PLys-b-PLeu) polymersomes for drug delivery applications.
• To evaluate the physicochemical properties, in vitro biodegradation, cellular uptake, cytotoxicity, and drug-loading/release characteristics of the developed polymersomes.
• To assess the in vitro anti-tumoral activity of irinotecan-loaded polymersomes against colorectal cancer cells.

Main Methods:

• Self-assembly of PLys-b-PLeu polymersomes with pH-dependent size control.
• In vitro biodegradation studies using enzymatic systems and human blood plasma.
• Cellular uptake studies using fluorescently labeled nanoparticles.
• Cytotoxicity assays on HEK, NIH-3T3, and A549 cell lines.
• Irinotecan encapsulation via pH gradient method and drug release kinetics analysis.
• In vitro anti-tumoral activity assessment on Caco-2 cells.

Main Results:

• PLys-b-PLeu polymersomes exhibited pH-dependent self-assembly, with sizes ranging from 180 to 650 nm.
• Nanoparticles demonstrated good biocompatibility, with no observed cytotoxicity up to 2 mg/mL.
• Successful encapsulation of irinotecan was achieved, with stable dispersion and controlled release profiles.
• Maximal drug loading capacity was determined to be 320±55 μg/mg of polymersomes.
• Irinotecan-loaded polymersomes showed significant in vitro anti-tumoral activity against Caco-2 cells.

Conclusions:

• PLys-b-PLeu polymersomes are promising nanocarriers for irinotecan delivery in colorectal cancer therapy.
• The developed polymersomes exhibit favorable characteristics including biocompatibility, controlled drug release, and potent anti-cancer activity.
• Further in vivo studies are warranted to explore the therapeutic potential of these nanocarriers.