Ultra‐pH‐Sensitive Biopolymer Micelles Based on Nuclear Base Pairs for Specific Tumor‐Targeted Drug Delivery

Abstract

AbstractThe nanocarriers modified with nonspecificity targeting groups can not only enrich in tumor sites, but can also accumulate in normal tissues to cause serious side effects. In order to ensure the therapeutic effects and overcome the side effects, herein, a ligand self‐detachment targeting system (mPEG‐T@A/VB7‐PCL micelles) based on hydrogen bond interaction between adenine (A) and thymine (T) for specific tumor targeting is developed. The nuclear magnetic spectrum shows that the successful introduction of biotin VB7 has no effect on formation and pH‐responsive property of the micelles. The cellular uptake experiment indicated these micelles can efficiently shield the non‐specificity targeting and can hardly be endocytosed by tumor cells in physiological environment. On the contrary, the detachment of poly(ethylene glycol) PEG crown which is triggered by hydrogen bond dissociation at tumor microenvironment pH 6.8 can enhance endocytosis due to the exposure of the VB7. Cytotoxicity assays show that the half maximal inhibitory concentration (IC50) of free doxorubicin DOX, DOX‐loaded mPEG‐T@A‐PCL (mPEG‐T@A‐PCL (DOX)), and mPEG‐T@A/VB7‐PCL (DOX) are about 2.03, 7.20, and 1.32 µg mL−1, respectively, which indicate that the mPEG‐T@A/VB7‐PCL (DOX) micelles can significantly improve the therapeutic effects. Accordingly, mPEG‐T@A/VB7‐PCL (DOX) micelles, as an innovative strategy, suggests feasibility of its broad applications in cancer therapy.