Preparation of pH-Responsive Doxorubicin Nanocapsules by Combining High-gravity Antisolvent Precipitation with In-situ Polymerization for Intracellular Anticancer Drug Delivery

Owing to the low pH value in tumor and cancer cells, drug delivery systems based on pH-responsive polymer nanocarriers have been extensively explored for anticancer chemotherapy. Herein, we developed a pH-responsive doxorubicin(DOX) nanocapsule(named as DNanoCapsule) prepared by combining in-situ polymerization technique with high-gravity antisolvent precipitation technique through an amphiphilic polymerized surface ligand. DNanoCapsules show an obvious spherical core-shell structure with a single DOX nanoparticle encapsulated in the polymer layer. Dissolution rate studies prove that the DNanoCapsules have robust drug-release profiles under acidic environments due to the division of the pH-sensitive cross-linker, which triggers the collapse of the polymer layer. The in vitro investigations demonstrated that the DNanoCapsules exhibited high cellular uptake efficiency and cytotoxicity for both HeLa and MCF-7 cancer cells. Therefore, this work may provide a promising strategy to design and develop various stimuli-responsive drug nanocapsules for the treatment of cancer or other diseases.