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

Biomacromolecules. 2023 Feb 13;24(2):849-857. doi: 10.1021/acs.biomac.2c01269. Epub 2023 Jan 13.

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, N.I.H., Extramural

MeSH terms

  • Antineoplastic Agents*
  • Cell Line, Tumor
  • Drug Delivery Systems
  • Humans
  • Immunoconjugates* / pharmacology
  • Immunoconjugates* / therapeutic use
  • Nanogels
  • Neoplasms* / drug therapy

Substances

  • Antineoplastic Agents
  • polyethylene glycol polyethyleneimine nanogel
  • Nanogels
  • Immunoconjugates