Cell Membrane-Anchored Click Reaction Enhances Porphyrin Uptake for Highly Efficient Photodynamic Therapy of Breast Tumors
Yu Ma, Xiaoyang Liu, Qiaochu Jiang, Haidong Xu, Guowei Liang, Guowei Liang, Wenjun Zhan, Xianbao Sun, Gaolin Liang, Gaolin Liang
Abstract
Enhancing cell uptake of drugs for better therapy is a fundamental scientific problem in pharmaceutics. The “hydrophobic–hydrophilic–hydrophobic” structure has shown the potential of enhancing cell uptake of drugs. Thus, cell membrane-anchored formation of this structure should additionally enhance cell uptake of drugs but has not been reported. In this work, we rationally designed acid-deshielding cysteine-PEG-DSPE ( DA-Cys-PD ) and PE-porphyrin-PEG-CBT ( Por-CBT ). After DA-Cys-PD anchors on the tumor cell membrane, the weak acidic environment of the cell deshields the anchor to yield Cys-PD, which subsequently click-reacts with Por-CBT to yield Por-Luc-PD with a “hydrophobic–hydrophilic–hydrophobic” structure. This in situ formed structure significantly enhances the cellular uptake of porphyrin and its consequent photodynamic therapeutic effect on breast tumors. Particularly, with the assistance of the cell membrane-anchored click reaction, porphyrin uptake in cancer cells or breast tumors is increased roughly to be 7.8-fold or 3.9-fold of that of the negative control group whose Cys is acid-inactive, respectively. The enhanced porphyrin uptake leads to highly efficient photodynamic therapy of breast tumors with a remarkable tumor growth inhibition rate of 64.1% compared with that of 5.5% of the negative control group. This approach of cell membrane-anchored click reaction provides people with a simple and feasible avenue for enhancing cell uptake of drugs/probes, as well as their therapeutic/diagnostic effects.