Sequential intracellular release of water-soluble cargos from Shell-crosslinked polymersomes

Area of Science:

• Nanotechnology and Materials Science
• Biomedical Engineering and Drug Delivery

Background:

• Polymersomes (PS) are nanostructures capable of encapsulating multiple cargos but struggle with sequential release.
• Controlled release of co-encapsulated hydrophilic molecules and hydrogels remains a significant challenge in drug delivery.

Purpose of the Study:

• To design and synthesize oxidation-responsive, shell-crosslinked polymersomes (PS) for controlled, sequential release of hydrophilic molecules and hydrogels.
• To investigate the in situ formation of hydrogels within PS and their impact on cargo release kinetics and cellular retention.

Main Methods:

• Fabrication of PS using amphiphilic brush block copolymers (POEGMA-POPSMA) via self-assembly.
• Co-loading of hydrophilic molecules and thermoresponsive poly(N-isopropylacrylamide) (PNIPAM) conjugates within the PS core.
• Induction of hydrogel formation via temperature increase above PNIPAM's LCST and control of shell permeability via oxidation.

Main Results:

• Achieved controlled, sequential release of molecular dyes and PNIPAM-based hydrogels by manipulating shell permeability through oxidation.
• Demonstrated successful in situ hydrogel formation within PS, leading to reduced leakage compared to molecular cargos.
• Observed enhanced intracellular accumulation and prolonged retention of hydrogels within live cells.

Conclusions:

• Integration of responsive hydrogels into crosslinkable PS offers a versatile platform for precise control over water-soluble cargo stability and release.
• This approach facilitates improved drug delivery by enhancing cargo retention and enabling sequential release strategies for complex therapeutic applications.