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
  • 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.
PMID: 36639133 DOI: 10.1021/acs.biomac.2c01269
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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