LAUSR

Immune checkpoint blockade of programmed cell death-ligand 1/programmed cell death-1 (PD-L1/PD-1) pathway via antibody is a potent strategy for T cells remodeling. Nevertheless, the potency of antibody is partly compromised by its high price, instability, risk of autoimmune disease, etc. Small molecule inhibitors are interesting alternatives to antibodies. However, tumor-specific delivery of small molecule inhibitor to the target site for boosting the interruption of PD-L1/PD-1 pathway is rarely reported. Herein, we designed a tumor-specific delivery nanoplatform that could efficiently deliver the small molecule inhibitor to the precise target site, greatly enhancing the blocking effect of PD-L1/PD-1 pathway. Hyaluronic acid (HA) was conjugated with chlorin e6 (Ce6), resulting in a HA-Ce6 conjugate (HC). The nanoplatform was constructed by the HC micelles with encapsulation of small molecule inhibitor BMS 202 (BMS) to form BMS/HC micelles. The target property of HA, combined with the hyaluronidase-induced degradation of HA in tumor site, enables the as-prepared micelles with tumor-specific delivery of BMS for blocking PD-L1/PD-1 pathway. Cooperative treatment with the photosensitizer Ce6, the present therapeutic nanoplatform demonstrated excellent photoimmunotherapy for tumor regression in distant tumors and lung metastasis. This strategy of tumor-specific delivery of small molecule inhibitors provides an effective pathway to strengthen the blocking efficacy of PD-L1/PD-1 on effective photoimmunotherapy.