Hypoxia-tropic Protein Nanocages for Modulation of Tumor- and Chemotherapy-Associated Hypoxia
journal contributionposted on 21.12.2018, 00:00 by 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
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.
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tumor progressionChemotherapy-Associated Hypoxiasurface-PEGylated FTnECMtarget hypoxic tumor cellsferritin nanocageshypoxia-tropic propertyhypoxic tumor tissuesendowing FTnnormoxic tumor areasHypoxia-tropic Protein Nanocagestumor extracellular matrixtumor hypoxiaHypoxia-inhibiting agents systemicallytreatment resistancetreatment regimens