Preparation and anti-tumor ability evaluation of anti-PD-L1 conjugated curcumin in colon cancer

Immune checkpoint inhibitors have been approved for various solid tumor treatments but have shown poor efficacy on colon cancer. Curcumin has been proven as an anti-tumor agent that inhibits cell cycle and tumor cell proliferation. Moreover, curcumin has also been reported to have the ability to inhibit PD-L1 expression, which might benefit the therapeutic efficacy of immune checkpoint inhibitors. Therefore, we proposed using antibodydrug conjugate (ADC) could effectively inhibit tumor proliferation and reverse the immunosuppression in colon cancer. We prepared an anti-PD-L1 conjugated curcumin with a ROS-responsive linker of phenylboronic acid carbamate, which provides chemo-drug active targeting ability and tumor environment-responsive release. Both in vitro and in vivo data confirm the improved cytotoxicity of anti-PD-L1-PBA-Cur and inhibited cell invasion. More importantly, the PD-L1 expression on the tumor surface was significantly reduced after being treated with ADC. The in vivo inhibition of tumor progression and PD-L1 expression was confirmed in both subcutaneous and in-suit mouse models. This study provides an effective colon treatment strategy with the advantages of high tumor targeting efficiency and immunopotentiation potential.