Active recruitment of anti-PD-1-conjugated platelets through tumor-selective thrombosis for enhanced anticancer immunotherapy

Immune checkpoint inhibitors (ICIs) can reinvigorate T cells to eradicate tumor cells, showing great potential in combating various types of tumors. We propose a delivery strategy to enhance tumor-selective ICI accumula-tion, which leverages the responsiveness of platelets and platelet-derivatives to coagulation cascade signals. A fused protein tTF-RGD targets tumor angiogenic blood vessel endothelial cells and initiates the coagulation locoregionally at the tumor site, forming a cellular hive to recruit anti-PD-1 antibody (aPD-1)-conjugated platelets to the tumor site and subsequently activating platelets to release aPD-1 antibody to reactivate T cells for improved immunotherapy. Moreover, on a patient-derived xenograft breast cancer model, the platelet membrane-coated nanoparticles can also respond to the coagulation signals initiated by tTF-RGD, thus enhanc-ing the accumulation and antitumor efficacy of the loaded chemotherapeutics. Our study illustrates a versatile platform technology to enhance the local accumulation of ICIs and chemodrugs by taking advantage of the responsiveness of platelets and platelet derivatives to thrombosis.

Automated summary

Immune checkpoint inhibitors (ICIs) have potential in treating various tumors by reinvigorating T cells. Researchers propose a delivery strategy to enhance tumor-selective ICI accumulation by utilizing platelet responsiveness to coagulation signals. A fused protein tTF-RGD targets tumor blood vessels and initiates local coagulation, attracting platelets conjugated with anti-PD-1 antibodies to release them for improved immunotherapy. The study also demonstrates enhanced accumulation and efficacy of chemotherapeutics using platelet membrane-coated nanoparticles. This versatile platform utilizes platelet responsiveness for improved local accumulation of ICIs and chemodrugs.