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


Journal

ACS nano
ISSN: 1936-086X
Titre abrégé: ACS Nano
Pays: United States
ID NLM: 101313589

Informations de publication

Date de publication:
22 01 2019
Historique:
pubmed: 24 12 2018
medline: 22 1 2020
entrez: 22 12 2018
Statut: ppublish

Résumé

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.

Identifiants

pubmed: 30576113
doi: 10.1021/acsnano.8b05399
pmc: PMC8323471
mid: NIHMS1726351
doi:

Substances chimiques

Antineoplastic Agents 0
Fluorescent Dyes 0
Nanocapsules 0
Polyethylene Glycols 3WJQ0SDW1A
Ferritins 9007-73-2
Cisplatin Q20Q21Q62J
Oxygen S88TT14065

Types de publication

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

Langues

eng

Sous-ensembles de citation

IM

Pagination

236-247

Subventions

Organisme : NEI NIH HHS
ID : P30 EY001765
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL125169
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL127413
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL136617
Pays : United States

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Auteurs

Xinglu Huang (X)

Key Laboratory of Bioactive Materials, Ministry of Education, College of Life Sciences, and State Key Laboratory of Medicinal Chemical Biology , Nankai University , Tianjin 300071 , China.
Center for Nanomedicine, Wilmer Eye Institute , Johns Hopkins University School of Medicine , Baltimore , Maryland 21231 , United States.
Department of Ophthalmology , Johns Hopkins University School of Medicine , Baltimore , Maryland 21231 , United States.

Jie Zhuang (J)

Cardiovascular Branch, National Heart, Lung, and Blood Institute , National Institutes of Health , Bethesda , Maryland 20892 , United States.

Seung Woo Chung (SW)

Center for Nanomedicine, Wilmer Eye Institute , Johns Hopkins University School of Medicine , Baltimore , Maryland 21231 , United States.
Department of Ophthalmology , Johns Hopkins University School of Medicine , Baltimore , Maryland 21231 , United States.

Buwei Huang (B)

Center for Nanomedicine, Wilmer Eye Institute , Johns Hopkins University School of Medicine , Baltimore , Maryland 21231 , United States.
Department of Biomedical Engineering , Johns Hopkins University School of Medicine , Baltimore , Maryland 21205 , United States.

Gilad Halpert (G)

Center for Nanomedicine, Wilmer Eye Institute , Johns Hopkins University School of Medicine , Baltimore , Maryland 21231 , United States.
Department of Ophthalmology , Johns Hopkins University School of Medicine , Baltimore , Maryland 21231 , United States.

Karina Negron (K)

Center for Nanomedicine, Wilmer Eye Institute , Johns Hopkins University School of Medicine , Baltimore , Maryland 21231 , United States.
Department of Pharmacology & Molecular Sciences , Johns Hopkins University , Baltimore , Maryland 21218 , United States.

Xuanrong Sun (X)

Center for Nanomedicine, Wilmer Eye Institute , Johns Hopkins University School of Medicine , Baltimore , Maryland 21231 , United States.
Department of Chemical & Biomolecular Engineering , Johns Hopkins University , Baltimore , Maryland 21218 , United States.
Collaborative Innovation Center of Yangtze River Delta Region Green Pharmaceuticals , Zhejiang University of Technology , Hangzhou 310014 , China.

Jun Yang (J)

Center for Nanomedicine, Wilmer Eye Institute , Johns Hopkins University School of Medicine , Baltimore , Maryland 21231 , United States.
Department of Chemical & Biomolecular Engineering , Johns Hopkins University , Baltimore , Maryland 21218 , United States.

Yumin Oh (Y)

Center for Nanomedicine, Wilmer Eye Institute , Johns Hopkins University School of Medicine , Baltimore , Maryland 21231 , United States.
The Russell H. Morgan Department of Radiology and Radiological Sciences , Johns Hopkins University School of Medicine , Baltimore , Maryland 21205 , United States.

Paul M Hwang (PM)

Cardiovascular Branch, National Heart, Lung, and Blood Institute , National Institutes of Health , Bethesda , Maryland 20892 , United States.

Justin Hanes (J)

Center for Nanomedicine, Wilmer Eye Institute , Johns Hopkins University School of Medicine , Baltimore , Maryland 21231 , United States.
Department of Ophthalmology , Johns Hopkins University School of Medicine , Baltimore , Maryland 21231 , United States.
Department of Biomedical Engineering , Johns Hopkins University School of Medicine , Baltimore , Maryland 21205 , United States.
Department of Pharmacology & Molecular Sciences , Johns Hopkins University , Baltimore , Maryland 21218 , United States.
Department of Chemical & Biomolecular Engineering , Johns Hopkins University , Baltimore , Maryland 21218 , United States.
Department of Oncology , Johns Hopkins University School of Medicine , Baltimore , Maryland 21205 , United States.

Jung Soo Suk (JS)

Center for Nanomedicine, Wilmer Eye Institute , Johns Hopkins University School of Medicine , Baltimore , Maryland 21231 , United States.
Department of Ophthalmology , Johns Hopkins University School of Medicine , Baltimore , Maryland 21231 , United States.

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Classifications MeSH