Dual-responsive hyaluronic acid-based hydrogel as a drug carrier for combined chemo-photodynamic therapy

Abstract

Single chemotherapy lacked controllability, while smart-responsive hydrogel could deliver drug to specific sites in response to different external stimuli. Hyaluronic acid–Chitosan–Thioketal@Chlorin e6 (HA-CS-TK@Ce6) hydrogel with dual response of ROS and hyaluronidase (HAase) was synthesized by electrostatic interaction force. HA-CS-TK@Ce6 hydrogel loaded with chemotherapeutic drug doxorubicin (DOX) and photosensitizer Ce6 successfully achieved the combined anticancer effect of chemotherapy and photodynamic therapy. Experimental results demonstrated that releasing efficiency of the hydrogel toward DOX could reach 90.6 % in pH = 5 H₂O₂ solution with HAase at T = 40 ℃. Moreover, HA-CS-TK@Ce6 hydrogel was capable of stimulating Ce6 to produce massive ROS under 650 nm laser irradiation, thus leading to breakage of ROS-cleavable TK and realizing degradation of hydrogel. It was worth mentioning that laser confocal results indicated that MCF-7 cells could successfully uptake Ce6 and DOX, which further proved that HA-CS-TK@Ce6 hydrogel could achieve efficient photodynamic-chemotherapeutic treatment. Therefore, dual-responsive HA-CS-TK@Ce6 hydrogel with excellent biocompatibility and degradability enabled selective and intelligent release of DOX, which would be prospective to improve therapeutic effect of cancer through chemo-photodynamic therapy.