Artificial nanoplatelet regulation of tumor immune microenvironment to inhibit post-surgical tumor recurrence and lung metastasis

Abstract

Tumor recurrence and metastasis are important causes of death in breast cancer patients after surgery. However, the nanomedicines are often difficult to accumulate and retain in residual microtumors because the surgery disrupts the original network of blood vessels in the solid tumor, which is a crucial factor leading to tumor recurrence and metastasis after surgery. Herein, an engineered artificial nanoplatelet (MOAP) was established by loading antigen protein ovalbumin (OVA) and PD-L1 inhibitor (aptamer-PD-L1) on MnOx nanoflowers and further coating with platelet membrane. MOAP can mimic platelets to participate in the coagulation process, target thrombus at the residual tumor site, and release OVA and Apt-PD-L1 under 808 nm laser irradiation to block immune checkpoint inhibition and prevent immune escape. Moreover, MnOx alleviated hypoxia, promoted the polarization of tumor-associated macrophages from M2 to M1 phenotype, and significantly reversed the tumor immunosuppressive microenvironment, thus enhancing the infiltration of cytotoxic T lymphocytes at the tumor site. In vivo experiments revealed that pre-surgery or post-surgery treatment of artificial platelets had a good anti-tumor effect, and inhibited tumor recurrence and lung metastasis after surgery, which demonstrated that MOAP is a suitable system for the treatment of post-surgery tumors.