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  2. Targeted Drug Delivery Using a Plug-to-Direct Antibody-Nanogel Conjugate

Targeted Drug Delivery Using a Plug-to-Direct Antibody-Nanogel Conjugate

  • Biomacromolecules. 2023 Jan 13. doi: 10.1021/acs.biomac.2c01269.
Uyen Huynh 1 Peidong Wu 1 Jingyi Qiu 2 Theeraphop Prachyathipsakul 1 Khushboo Singh 1 D Joseph Jerry 3 4 Jingjing Gao 1 S Thayumanavan 1 2 3
Affiliations

Affiliations

  • 1 Department of Chemistry, University of Massachusetts, Amherst, Massachusetts 01003, United States.
  • 2 Department of Biomedical Engineering, University of Massachusetts, Amherst, Massachusetts 01003, United States.
  • 3 Center for Bioactive Delivery, Institute for Applied Life Sciences, University of Massachusetts, Amherst, Massachusetts 01003, United States.
  • 4 Department of Veterinary and Animal Sciences, University of Massachusetts, Amherst, Massachusetts 01003, United States.
Abstract

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.

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