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
P-selectin. Compared 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 4T1 spontaneous
metastasis model. In addition, due to the contribution of
fucoidan, FD/DOX treatment 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.