A bifunctional agent for efficient imaging of PD-L1 and antimelanoma activity.

Immune checkpoint inhibitors targeting PD-L1 lead to challenging patterns of efficacy and toxicity. Herein, by focusing on tracing the molecular biomarker of response to efficacy, we formulated a central hypothesis for the construction of theranostic functional monoclonal antibody incorporation with tracing ability based on fluorescence turn-on and controllable release strategies. Functional atezolizumab was constructed by in situ assembly of both biorthogonal group and controllable release group. The theranostic monoclonal antibodies achieved quantitative monitoring of PD-L1 on cells with different expression levels through biorthogonal light-up fluorescence, followed by the release of atezolizumab in combination with high tumor reduction conditions to promote immune activation. The combination of bio-orthogonal reaction-driven fluorescence turn-on and tumor microenvironment-responsive controllable release afforded theranostic bifunctional monoclonal antibodies for the detection of PD-L1 and combination therapy. Remarkably, these novel theranostics might be used as probes for fluorescent imaging and simultaneously achieving potent antitumor efficacy.