Open AccessHypoxia-tropic Protein Nanocages for Modulation of Tumor- and Chemotherapy-Associated Hypoxia
Author(s) -
Xinglu Huang,
Jie Zhuang,
Soo Kyo Chung,
Bu-Wei Huang,
Gilad Halpert,
Kariegron,
Xuanrong Sun,
Jun Yang,
You-Take Oh,
Paul M. Hwang,
Justin Hanes
Publication year - 2018
Publication title -
acs nano
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.554
H-Index - 382
eISSN - 1936-086X
pISSN - 1936-0851
DOI - 10.1021/acsnano.8b05399
Subject(s) - nanocages , hypoxia (environmental) , tumor hypoxia , cancer research , extracellular matrix , tumor microenvironment , chemotherapy , pharmacology , medicine , materials science , chemistry , microbiology and biotechnology , tumor cells , biology , radiation therapy , biochemistry , oxygen , organic chemistry , catalysis
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.