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Fucoidan-functionalized activated platelet-hitchhiking micelles simultaneously track tumor cells and remodel the immunosuppressive microenvironment for efficient metastatic cancer treatment

引用

Acta Pharmaceutica Sinica B 2022年第1期12卷 467-482页

作者： Rong Guo Miao Deng Xuan He Mengmeng Li Jiaxin Li Penghui He Houqin Liu Man Li Zhirong Zhang Qin He Key Laboratory of Drug-Targeting and Drug Delivery System of the Education Ministry and Sichuan Province Sichuan Engineering Laboratory for Plant-Sourced Drug and Sichuan Research Center for Drug Precision Industrial TechnologyWest China School of PharmacySichuan UniversityChengdu 610041China

Tumor metastasis is responsible for most mortality in cancer patients, and remains a challenge in clinical cancer treatment. platelets can be recruited and activated by tumor cells, then adhere to circulating tumor cells(CTCs) and assist tumor cells extravasate in distant organs. Therefore, nanoparticles specially hitchhiking on activated platelets are considered to have excellent targeting ability for primary tumor, CTCs and metastasis in distant organs. However, the activated tumor-homing platelets will release transforming growth factor-β(TGF-β), which promotes tumor metastasis and forms immunosuppressive microenvironment. Therefore, a multitalent strategy is needed to balance the accurate tumor tracking and alleviate the immunosuppressive signals. In this study, a fucoidan-functionalized micelle(FD/DOX) was constructed, which could efficiently adhere to activated platelets through *** with the micelle without P-selectin targeting effect, FD/DOX had increased distribution in both tumor tissue and metastasis niche, and exhibited excellent anti-tumor and anti-metastasis efficacy on 4 T1 spontaneous metastasis model. In addition, due to the contribution of fucoidan, FD/DOXtreatment was confirmed to inhibit the expression of TGF-β, thereby stimulating anti-tumor immune response and reversing the immunosuppressive microenvironment. The fucoidan-functionalized activated platelets-hitchhiking micelle was promising for the metastatic cancer treatment.

关键词： Fucoidan activated platelets P-selectin platelets-hitchhiking Track tumor cells TGF-β Reverse immunosuppressive microenvironment Tumor metastasis

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