Uniformly sized hollow microspheres loaded with polydopamine nanoparticles and doxorubicin for local chemo-photothermal combination therapy

Abstract

Techniques to improve the accumulation of therapeutic agents in tumors, which subsequently enhance the therapeutic efficacy of anticancer drugs against malignant tumors and reduce their side effects remains a great challenge. Here, we developed a hollow biodegradable polymer microsphere, in which the interior hollow space was loaded with polydopamine (PDA) nanoparticles and doxorubicin hydrochloride (DOX·HCl) and the outer shell layer was biodegradable polymer poly(lactide-co-glycolide) (PLGA). We produced these microspheres with coaxial electrospraying technology for enhanced local chemo-photothermal combination therapy. The microspheres with a uniform size have high photothermal conversion efficiency and high photostability. When these microspheres were intratumorally injected into tumor-bearing mice, a local hyperthermia effect was immediately generated from the PDA nanoparticles in these microspheres using near-infrared light irradiation at the tumor site. Simultaneously, the loaded DOX·HCl was rapidly released due to photothermy and diffusion into the cells. Compared with intravenously injected nanomedicines, an extremely high content of DOX·HCl in the tumor is achieved, with over ~22% at 6 h after intratumoral injection of the microspheres. Therefore, synergism between the photothermal therapy and chemotherapy will accelerate cell apoptosis, significantly enhance treatment efficacy and decrease the side effects to normal tissues. The intratumoral administration of therapeutic agents possesses more advantages than systemic chemotherapy. The hollow structured microspheres have great potential application as a drug delivery system due to their unique features.