Coiled-Coil Protein Hydrogels Engineered with Minimized Fiber Diameters for Sustained Release of Doxorubicin in Triple-Negative Breast Cancer

Dustin Britton, Jakub Legocki, Deven Paul, Olga Katsara, Orlando Aristizabal, Neelam Pandya, Orin Mishkit, Yingxin Xiao, Matias Aristizabal, Neha Rahman, Robert Schneider, Youssef Z. Wadghiri, Jin Kim Montclare

Research output: Contribution to journalArticlepeer-review

Abstract

Triple-negative breast cancer (TNBC) lacks expressed protein targets, making therapy development challenging. Hydrogels offer a promising new route in this regard by improving the chemotherapeutic efficacy through increased solubility and sustained release. Moreover, subcutaneous hydrogel administration reduces patient burden by requiring less therapy and shorter treatment times. We recently established the design principles for the supramolecular assembly of single-domain coiled-coils into hydrogels. Using a modified computational design algorithm, we designed Q8, a hydrogel with rapid assembly for faster therapeutic hydrogel preparation. Q8 encapsulates and releases doxorubicin (Dox), enabling localized sustained release via subcutaneous injection. Remarkably, a single subcutaneous injection of Dox-laden Q8 (Q8•Dox) significantly suppresses tumors within just 1 week. This work showcases the bottom-up engineering of a fully protein-based drug delivery vehicle for improved TBNC treatment via noninvasive localized therapy.

Original languageEnglish (US)
JournalACS Biomaterials Science and Engineering
DOIs
StateAccepted/In press - 2024

Keywords

  • computational design
  • drug delivery
  • hydrogel
  • protein engineering
  • triple negative breast cancer

ASJC Scopus subject areas

  • Biomaterials
  • Biomedical Engineering

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