A ROS-Stimulus-Responsive Nanocarrier Loading with Guanidine-Modified Hydroxycamptothecin Prodrug for Enhanced Anti-Tumor Efficacy

We report a reactive oxygen species (ROS)stimulus-responsive phenylboronic acid pinacol ester nanocarrier, loaded with guanidine-modified 10-hydroxycamptothecin (HCPT) prodrug, to create a drug delivery-base nanomedicine. The prodrug was stuck tightly in the nanocarrier with over 99% drug-loading efficiency due to the superposition of hydrogen bonds from guanidine and carboxyl, hydrophobic interaction, p-p stacking interaction from phenylboronic acid pinacol ester, and the HCPT prodrug. The aqueous stability of the phenylboronic acid pinacol ester nanocarrier improved remarkably after drug loading because of the interaction between the prodrug and the nanocarrier. Thus, the nanomedicine could realize ROS-triggered disassembly at the tumor sites, release the cell-penetrating prodrug, and achieve improved cellular uptake than the HCPT alone. The results of in vivo antitumor determination demonstrated three-fold inhibition of tumor growth rate of the ROS-stimulus-responsive nanomedicine, compared with HCPT, and the side effects of the prodrug complex reduced significantly. Therefore, our approach offers a promising strategy for the enhancement of antitumor efficacy.