Negative Surface Shielded Polymeric Micelles with Colloidal Stability for Intracellular Endosomal/Lysosomal Escape

Area of Science:

• Biomedical Engineering
• Materials Science
• Oncology

Background:

• Effective antitumor therapies rely on efficient endosomal escape for intracellular drug delivery.
• Conventional approaches often face colloidal instability due to protein interactions with positively charged surfaces.

Purpose of the Study:

• To develop a novel drug delivery system that overcomes colloidal instability and facilitates endosomal escape for enhanced cancer therapy.
• To investigate the properties and therapeutic efficacy of negatively charged surface-shielded polymeric micelles.

Main Methods:

• Construction of negatively charged surface-shielded polymeric micelles using polymethylacrylamide derivatives and chitosan.
• Loading micelles with doxorubicin (DOX) to create CSO-SS-PDPA/DOX nanoparticles.
• Evaluation of colloidal stability, protein corona formation, endosomal escape, and drug release kinetics.
• Assessment of therapeutic efficacy in 3D tumor spheroids and a mouse model.

Main Results:

• The developed micelles (CSO-SS-PDPA/DOX) maintained a negative surface charge, resisting protein corona formation.
• Efficient and rapid endosomal escape was observed within minutes.
• Redox-responsive drug release was confirmed.
• Superior therapeutic efficacy was demonstrated in both 3D tumor spheroids and in vivo models.

Conclusions:

• The negatively charged surface-shielded polymeric micelles offer a promising strategy for stable drug delivery.
• This approach effectively achieves intracellular endosomal/lysosomal escape, enhancing antitumor therapeutic outcomes.
• The developed system presents new avenues for advanced drug delivery applications in cancer treatment.