Laser-Responsive Polymeric Nanomicelles to Subdue Tumor Multidrug Resistance Based on Mild Photodynamic Therapy and Chemotherapy

Photodynamic therapy (PDT) is a promising treatment strategy that has shown great potential to subdue tumor’s multidrug resistance (MDR). However, their inevitable phototoxicity may damage key normal tissues or major blood vessels. Herein, we report a bifunctional drug-delivery system based on chlorin e6 (Ce6)–doxorubicin (DOX)–poly(phosphorylcholine) nanomicelles, which was able to combine mild PDT (mPDT, less damage to cells and tissues) with chemotherapy to reverse MDR. First, a PDT-responsive nanomicelle, DOX-conjugated polymer micelles encapsulating the photosensitizer Ce6 (Ce6/pMPC-DOX), is synthesized. Upon low-level near-IR laser irradiation, the lower concentration of ROS generated by Ce6/pMPC-DOX nanomicelles is quantitatively and functionally sufficient to effectively inhibit P-glycoprotein and sensitize MDR cells to chemodrugs without extra damage (mPDT effect). Additionally, further experimental results confirm that the synergistic therapy of mPDT and chemotherapy can eradicate a multidrug-resistant tumor in vivo safely and effectively.