1. Academic Validation
  2. A bifunctional agent for efficient imaging of PD-L1 and antimelanoma activity

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

  • Bioorg Chem. 2023 Oct 11:141:106912. doi: 10.1016/j.bioorg.2023.106912.
Jin Wang 1 Xiaoyan Pan 1 Ping Hai 2 Yongbiao Zheng 2 Jie Zhang 3 Yuanyuan Shan 4
Affiliations

Affiliations

  • 1 School of Pharmacy, Health Science Center, Xi'an Jiaotong University, Xi'an 710061, China.
  • 2 NMPA Key Laboratory for Quality Control of Traditional Chinese and Tibetan Medicine, Qinghai Provincial Drug Inspection and Testing Institute, Xining 810016, China.
  • 3 School of Pharmacy, Health Science Center, Xi'an Jiaotong University, Xi'an 710061, China. Electronic address: zhj8623@mail.xjtu.edu.cn.
  • 4 Department of Pharmacy, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710061, China. Electronic address: yuanssyuan@163.com.
Abstract

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.

Keywords

Biorthogonal reaction; Fluorescence turn on; Immune checkpoint inhibitors; Release; Theranostic.

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