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The employment of antibodies as a targeted drug delivery vehicle has proven successful which is exemplified by the emergence of antibody–drug conjugates (ADCs). However, ADCs are not without their shortcomings. Improvements may be made to the ADC platform by decoupling the cytotoxic drug from the delivery vehicle and conjugating an organometallic catalyst in its place. The resulting protein–metal catalyst conjugate was designed to uncage the masked cytotoxin administered as a separate entity. Macropinocytosis of albumin by cancerous cells suggests the potential of albumin acting as the tumor-targeting delivery vehicle. Herein reported are the first preparation and demonstration of ruthenium catalysts with cyclopentadienyl and quinoline-based ligands conjugated to albumin. The effective uncaging abilities were demonstrated on allyloxy carbamate (alloc)-protected rhodamine 110 and doxorubicin, providing a promising catalytic scaffold for the advancement of selective drug delivery methods in the future. 

Metal-mediated chemical reactions have been a vital area of research for over a century. Recently, there has been increasing effort to improve the performance of metal-mediated catalysis by optimizing the structure and chemical environment of active catalytic species towards process intensification and sustainability. Network-supported catalysts use a solid (rigid or flexible) support with embedded metal catalysts, ideally allowing for efficient precursor access to the catalytic sites and simultaneously not requiring a catalyst separation step following the reaction with minimal catalyst leaching. This minireview focuses on recent developments of network-supported catalysts to improve the performance of a wide range of metal-mediated catalytic reactions. We discuss in detail the different strategies to realize the combined benefits of homogeneous and heterogeneous catalysis in a metal catalyst support. We outline the unique versatility, tunability, properties, and activity of such hybrid catalysts in batch and continuous flow configurations. Furthermore, we present potential future directions to address some of the challenges and shortcomings of current flexible network-supported catalysts.