Nature子刊：北京大学刘志博团队开发邻近疗法药物肿瘤原位合成新策略

Core Viewpoint - The article discusses a novel cancer treatment strategy called "Decaging-to-Ligation" (D2L), which enables precise recruitment of proteins or immune cells to tumor sites, significantly inhibiting tumor growth while minimizing systemic toxicity [3][12]. Group 1: Research Findings - The study successfully synthesized proteolysis-targeting chimeras (PROTAC) in tumor-localized concentrations sufficient for effective target protein degradation, leading to a 14.8-fold increase in T cell activation levels [2][10]. - The D2L strategy effectively overcomes On-target Off-tumor (OTOT) toxicity, a major barrier for therapies like PROTAC and T cell-mediated immunotherapy [5][12]. - The research team demonstrated the feasibility of the D2L strategy by achieving selective imaging of FAP-positive cells and successfully degrading the target protein BRD4 in tumors with minimal toxicity to the small intestine [10][12]. Group 2: Technological Innovations - The D2L strategy represents an innovative approach in the intersection of chemical biology and drug discovery, facilitating tumor-selective reactions that can induce proximity effects between proteins and cells [7][12]. - The study highlights the potential of bioorthogonal chemistry in achieving selective drug release at tumor sites, bridging the gap between bioorthogonal connection technology and tumor-selective regulation [6][12]. Group 3: Implications for Cancer Treatment - The D2L strategy is positioned as a promising platform for precise cancer treatment, aiming to activate therapeutic assemblies in vivo and address critical limitations of proximity-mediated cancer therapies [12].