Engineering Platelets with PDL1 Antibodies and Iron Oxide Nanoparticles for Postsurgical Cancer Immunotherapy

Abstract

Recently, immune checkpoint blockade (ICB) therapy has achieved great success in inhibition of the recurrence and metastasis of tumor. However, this therapy is challenged by the poor delivery efficiency of ICB agents and the insufficient activation of antitumor immunity by ICB only. Here, we describe a strategy using platelets as carriers for co-delivery of ICB agents (anti-PDL1 antibodies, aPDL1) and photothermal agents (iron oxide nanoparticles, IONPs) to the postsurgical tumor site, which simultaneously provides photothermal therapy for ablation of residual tumor cells and ICB therapy for blocking the immunoinhibitory signals in the tumor microenvironment. We engineered platelets by chemical conjugation of aPDL1 and physical adsorption of IONPs on the surfaces of the platelets. Once they were adhered to the subendothelium of the surgical site, engineered platelets (P-P-IO) were activated and released aPDL1 and IONPs to the surrounding tissue. Upon laser irradiation, mild photothermal therapy (PTT) induces necrosis of residual tumor cells, producing tumor-associated antigens to generate innate immune responses. The co-delivered aPDL1 leads to efficient antitumor immunity, as evidenced by the reduced recurrence of the residual tumor and improved infiltration of both CD4+ and CD8+ T cells in a postsurgical breast tumor xenograft mouse model. We believe our strategy holds great promise in the clinic for combating postsurgical cancer recurrence.

Keywords: cancer immunotherapy; drug delivery; magnetic nanoparticles; photothermal therapy; platelets.