Dual-Responsive Polymer Micelles for Target-Cell-Specific Anticancer Drug Delivery

Citations Over TimeTop 1% of 2014 papers

Abstract

Efficient delivery of therapeutic agents with nanocarriers into the nucleus to achieve high therapeutic efficiency is still a major challenge for cancer therapy due to mucosal barriers, nonspecific uptake, and intracellular drug resistance. In this study, we develop a dual-responsive polymer micelle system with sheddable polyethylenimine (PEI) shells for actively targeted drug delivery. This system exhibits an ultrasensitive negative-to-positive charge reversal in response to the extracellular pH value, resulting in greatly enhanced uptake by cancer cells via electrostatic interaction. Moreover, the active targeting ability can further promote the selective uptake of the nanocarriers in the cancer cell. Once the micelles escape from the lysosomes, the disulfide linkages can be cleaved by GSH in the cytoplasm, and in turn the hydrophilic PEI shell is deshielded, leading to the rapid release of the encapsulated agent into the nuclei. The antitumor activity in 4T1 tumor-bearing mice reveals that this novel system possesses a long blood circulation due to the originally negatively charged surface and can significantly promote the cell internalization and intracellular drug release, thus leading to a high therapeutic efficacy against resistant tumors and fewer side effects to normal tissues.

Related Papers

• → Design and Fabrication of Magnetically Responsive Nanocarriers for Drug Delivery(2016)83 cited
• → Application and Perspective of pH-Responsive Nano Drug Delivery Systems(2018)23 cited
• → An effective polymeric nanocarrier that allows for active targeting and selective drug delivery in cell coculture systems(2021)10 cited
• → Polyethylenimine Functionalized Ultrasmall Mesoporous Silica Nanoparticles for siRNA Delivery(2022)10 cited
• → Targeted Drug Delivery(2018)3 cited