biostudies-literatureHuynh UNational Institute of General Medical SciencesNIGMS NIH HHS849-857https://www.ebi.ac.uk/biostudies/studies/S-EPMC9928872biostudies-literatureUnknown24(2)Targeted drug delivery using antibody-drug conjugates has attracted great attention due to its enhanced therapeutic efficacy compared to traditional chemotherapy. However, the development has been limited due to a low drug-to-antibody ratio and laborious linker-payload optimization. Herein, we present a simple and efficient strategy to combine the favorable features of polymeric nanocarriers with antibodies to generate an antibody-nanogel conjugate (ANC) platform for targeted delivery of cytotoxic agents. Our nanogels stably encapsulate several chemotherapeutic agents with a wide range of mechanisms of action and solubility. We showcase the targetability of ANCs and their selective killing of cancer cells over-expressing disease-relevant antigens such as human epidermal growth factor receptor 2, epidermal growth factor receptor, and tumor-specific mucin 1, which cover a broad range of breast cancer cell types while maintaining low to no toxicity to non-targeted cells. Overall, our system represents a versatile approach that could impact next-generation nanomedicine in antibody-targeted therapeutics.BiomacromoleculesTargeted Drug Delivery Using a Plug-to-Direct Antibody-Nanogel Conjugate.PMC9928872GM-136395T32 GM135096R35 GM136395Qiu JSingh KWu PGao JThayumanavan SPrachyathipsakul TJerry DJHuynh UfalseTargeted Drug Delivery Using a Plug-to-Direct Antibody-Nanogel Conjugate.Targeted drug delivery using antibody-drug conjugates has attracted great attention due to its enhanced therapeutic efficacy compared to traditional chemotherapy. However, the development has been limited due to a low drug-to-antibody ratio and laborious linker-payload optimization. Herein, we present a simple and efficient strategy to combine the favorable features of polymeric nanocarriers with antibodies to generate an antibody-nanogel conjugate (ANC) platform for targeted delivery of cytotoxic agents. Our nanogels stably encapsulate several chemotherapeutic agents with a wide range of mechanisms of action and solubility. We showcase the targetability of ANCs and their selective killing of cancer cells over-expressing disease-relevant antigens such as human epidermal growth factor receptor 2, epidermal growth factor receptor, and tumor-specific mucin 1, which cover a broad range of breast cancer cell types while maintaining low to no toxicity to non-targeted cells. Overall, our system represents a versatile approach that could impact next-generation nanomedicine in antibody-targeted therapeutics.2023-01-01T00:00:00Z2023 Feb2025-04-03T23:51:04.866Z2025-04-03T23:51:04.866ZS-EPMC99288723663913310.1021/acs.biomac.2c01269