Study on the application of hollow mesoporous polydopamine as a nanoparticle drug carrier in tumor combination therapy

Abstract

In combination therapy for tumors, combined components can play synergistic roles while leveraging their respective therapeutic advantages, but there are still some challenges in the development of nanomaterials for multimodal combination therapy for tumors. In this study, a novel targeted nanoparticle drug-delivery platform (HMPDA@Ce6/DOX@AMC) based on hollow mesoporous polydopamine (HMPDA) was designed for the synergistic treatment of tumors. HMPDA with a cavity structure was used to load the anticancer drug doxorubicin hydrochloride (DOX) and the photosensitizer chlorin e6 (Ce6). In the acidic tumor microenvironment, under the irradiation of a 660 nm laser, the carrier released Ce6 and DOX as a rapid response while producing cytotoxic reactive oxygen species (ROS). Next, the immunomodulator CpG, anticancer gene miR-145, and S6-aptamer were linked and named as AMC. The S6-aptamer was used for the accurate targeting of chemotherapy drugs to target cancer cells, and CpG was used for immunotherapy (IMT) by enhancing anti-tumor immune response. It was found that the average loading of DOX and Ce6 on the nanocarriers reached 242.65 mg g⁻¹ and 90.86 mg g⁻¹, respectively. Using the indicator 1,3-diphenylisobenzofuran (DPBF), it was detected that the prepared nanocarriers could produce ROS under the irradiation of a specific laser wavelength, and the yield was positively correlated with the irradiation time. Cytotoxicity experiments showed that the nanocarriers had an obvious inhibitory effect on 4T1 cells. The designed nanodrug-delivery system had a stronger tumor inhibition ability than single therapies under the combination of multiple therapies and is expected to achieve accurate targeting and enhanced treatment of early tumors.