Reshaping Antitumor Immunity with Chemo‐Photothermal Integrated Nanoplatform to Augment Checkpoint Blockade‐Based Cancer Therapy

Abstract

AbstractImmune checkpoint therapy promotes cytotoxic T lymphocytes (CTLs) activity to eliminate tumors. Nevertheless, their effectiveness in solid tumors is limited by inadequate infiltration of CTLs and suppressive tumor microenvironment (TME). Herein, an anti‐PD‐1 antibody coupled chemo‐photothermal integrated nanoplatform (A/Au@MSMs‐P) is proposed to reshape antitumor immunity against cancer. The matrix metalloproteinase‐2 (MMP‐2) responsive A/Au@MSMs‐P promotes the separation of abemaciclib‐loaded gold‐silica nanoparticles (A/Au@MSMs) and anti‐PD‐1 antibody, achieving a triple‐coordinated strategy to enhance checkpoint blockade therapy. First, chemo‐photothermal therapy of A/Au@MSMs induces cell cycle arrest in G1 phase and promotes tumor cells apoptosis to achieve local ablation. Second, immunogenic death of tumor cells promotes the maturation of dendritic cells and recruits antigen‐specific CTLs into tumor tissue to promote immune activation. Third, abemaciclib markedly suppresses the proliferation of regulatory T cells (Tregs) to alleviate the immunosuppression of the TME and potentiates the effectiveness of CTLs. This triple‐coordinated strategy not only reshapes the antitumor immunity to enhance checkpoint blockade, but also cooperates with chemo‐photothermal therapy, leading to improved antitumor efficiency and prolonged survival rate. Taken together, this study presents a promising strategy for improving checkpoint therapy response and has great potential in future cancer therapy.