Combination therapy for tumors can play a synergistic role 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 synergistic treatment of tumors. HMPDA with cavity structure were used to load the anticancer drug doxorubicin hydrochloride (DOX) and the photosensitizer Chlorin e6 (Ce6). In the acidic tumor microenvironment, under the irradiation with 660 nm laser, the carrier would release Ce6 and DOX in a rapid response, while producing cytotoxic reactive oxygen species (ROS). Then, the immunomodulator CpG, the anti-cancer gene miR-145 and S6-Aptamer were linked, which were named AMC. S6-Aptamer was used for chemotherapy drugs to accurately 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 on nanocarriers reached 242.65 mg/g. Using the indicator 1, 3-diphenylisobenzofuran (DPBF), it was detected that the prepared nanocarriers could produce ROS under the irradiation of a specific wavelength of laser, and the yield was positively correlated with the irradiation time. The cytotoxicity experiments showed that the nanocarriers had obvious inhibitory effect on 4T1 cells. The designed nano drug delivery system had stronger tumor inhibition ability than single therapy under the combination of multiple therapies, and is expected to achieve accurate targeting and enhanced treatment of early tumors.

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