pH-responsive dual-drug nanomicelles for co-delivery of DOX and Ce6 for combination therapy of tumors

In this study, pH-responsive nanomicelles were constructed to co-deliver the chemotherapeutic drug doxorubicin (DOX) and the photosensitizer chlorin e6 (Ce6). The nanomicelles can deliver both drugs loaded to the tumor site, achieving synergy between chemotherapy and photodynamic therapy. Using polyethylene glycol as a carrier, DOX was grafted onto the carrier by pH-sensitive hydrazone bonding to obtain amphiphilic polymericprodrug. Ultrasonic self-assembly was used to fabricate single-drug nanomicelles M(DOX), and Ce6 was loaded into the hydrophobic core to prepare dual-drug nanomicelles M(Ce6/DOX). The nanomicelles showed pH-sensitive drug release behavior, with 73.03% DOX release and 68.98% Ce6 release within 48 h. The dual-drug nanomicelles can significantly produce ROS under the excitation of 660 nm laser source as detected by the ROS detection probe. The nanomicelles showed significant cytotoxicity against HeLa cells and less cytotoxicity against L929 cells. In the intracellular ROS detection experiment, the dual-drug nanomicelles produced significant ROS, indicating that the nanomicelles can achieve photodynamic therapeutic effects. In conclusion, these nanomicelles provide a novel idea on the combinatorial utilization of chemotherapy and photodynamic therapy.