A ROS-response hyaluronic acid-coated/chitosan polymer prodrug for enhanced tumour targeting efficacy of SN38

Abstract

Ethyl-10-hydroxycamptothecin (SN38) is a camptothecin derivative with significant anti-tumour therapeutic potential, while the clinical application of SN38 was limited by its poor water solubility and low stability. Herein, a core-shell polymer prodrug hyaluronic acid @chitosan-S-SN38 (HA@CS-S-SN38) was designed by CS-S-SN38 as the core and the HA as the shell, which aims to overcome the limitations of the clinical application of SN38, while realising the high tumour targeting of polymer prodrug and the controllable release of drug in tumour cells. HA@CS-S-SN38 showed the high responsiveness of the tumour microenvironment and the safe stability of blood circulation. Furthermore, HA@CS-S-SN38 exhibited the begin uptake efficiency and favourable apoptosis in the 4T1 cells. More importantly, compared with irinotecan hydrochloride trihydrate (CPT-11), HA@CS-S-SN38 significantly improved the conversion efficiency of the prodrug to SN38, and showed excellent tumour targeting and retention in vivo by combining passive and active targeting strategies. In tumour-bearing mice treatment, HA@CS-S-SN38 showed the perfect anti-tumour effect and therapeutic safety. These results indicated that the polymer prodrug designed by ROS-response/HA-modification strategy is a safe and efficient drug delivery system, which provides a new idea for clinical utilisation of SN38 and warrants further evaluation.