Functionalization of Active Ester-Based Polymersomes for Enhanced Cell Uptake and Stimuli-Responsive Cargo Release

Area of Science:

• Polymer Chemistry
• Nanotechnology
• Biomedical Engineering

Background:

• Amphiphilic block copolymers based on poly(2,3-dihydroxypropyl methacrylamide) (P(DHPMA)) can self-assemble into polymer vesicles (polymersomes).
• Existing polymersomes offer a stable platform for drug delivery but often lack targeted release mechanisms and specific cellular targeting capabilities.

Purpose of the Study:

• To engineer P(DHPMA)-based polymersomes with pH-dependent disintegration for controlled cargo release.
• To incorporate mannose targeting units into the hydrophilic block for enhanced and selective targeting of dendritic cells.
• To evaluate the stability, cytotoxicity, and cargo release efficiency of the modified polymersomes.

Main Methods:

• Synthesis of amphiphilic block copolymers incorporating pH-sensitive units (2-(2,2-dimethyl-1,3-dioxolane-4-yl)ethyl methacrylate) and mannose targeting moieties.
• Formation and characterization of polymersomes using dynamic light scattering (DLS).
• Assessment of polymersome stability against Triton X-100 and evaluation of their cytotoxicity.
• Demonstration of pH-triggered cargo release using an enzyme (glucose oxidase) and assessment of targeting efficiency to dendritic cells.

Main Results:

• Polymersomes were successfully formed and demonstrated stability against detergents like Triton X-100.
• Incorporation of specific monomers enabled pH-dependent disintegration of the polymersome membrane, facilitating cargo release.
• The presence of mannose on the hydrophilic block led to enhanced and selective targeting of dendritic cells.
• The polymersomes exhibited low cytotoxicity, indicating their potential biocompatibility.

Conclusions:

• The developed P(DHPMA)-based polymersomes are stable, biocompatible, and possess tunable properties for targeted drug delivery.
• pH-responsive disintegration allows for controlled release of encapsulated cargo, such as enzymes.
• Mannose functionalization enables specific targeting of dendritic cells, opening avenues for targeted immunotherapies and diagnostics.