Hypoxia-tropic Protein Nanocages for Modulation of Tumor- and Chemotherapy-Associated Hypoxia

Xinglu Huang, Jie Zhuang, Seung Woo Chung, Buwei Huang, Gilad Halpert, Karina Negron, Xuanrong Sun, Jun Yang, Yumin Oh, Paul M. Hwang, Justin Hanes, Jung Soo Suk

Research output: Contribution to journalArticle

Abstract

Despite its central role in tumor progression and treatment resistance, poor vascularization that necessitates penetration of therapeutics through tumor extracellular matrix (ECM) constitutes a significant challenge to managing tumor hypoxia via conventional systemic treatment regimens. In addition, methods to target hypoxic tumor cells are lacking. Here, we discovered that human ferritin nanocages (FTn) possess an intrinsic ability to preferentially engage with hypoxic tumor tissues, in addition to normoxic tumor areas. We also developed a simple method of endowing FTn with spatially controlled "mosaic" surface poly(ethylene glycol) (PEG) coatings that facilitate deep penetration of FTn through ECM to reach hypoxic tumor tissues while retaining its inherent hypoxia-tropic property. Hypoxia-inhibiting agents systemically delivered via this surface-PEGylated FTn were readily accumulated in hypoxic tumor tissues, thereby providing significantly enhanced therapeutic benefits compared to the identical agents delivered in solution as a stand-alone therapy or an adjuvant to restore efficacy of conventional systemic chemotherapy.

Original languageEnglish (US)
Pages (from-to)236-247
Number of pages12
JournalACS Nano
Volume13
Issue number1
DOIs
StatePublished - Jan 22 2019

Keywords

  • HIF-1α
  • PEGylation
  • drug resistance
  • ferritin nanocage
  • hypoxia
  • tumor penetration

ASJC Scopus subject areas

  • Materials Science(all)
  • Engineering(all)
  • Physics and Astronomy(all)

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  • Cite this

    Huang, X., Zhuang, J., Chung, S. W., Huang, B., Halpert, G., Negron, K., Sun, X., Yang, J., Oh, Y., Hwang, P. M., Hanes, J., & Suk, J. S. (2019). Hypoxia-tropic Protein Nanocages for Modulation of Tumor- and Chemotherapy-Associated Hypoxia. ACS Nano, 13(1), 236-247. https://doi.org/10.1021/acsnano.8b05399