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Tumor-Penetrating Nanoparticles for Enhanced Anticancer Activity of Combined Photodynamic and Hypoxia-Activated Therapy. ACS Nano 2017 Feb 28;11(2):2227-2238

Date

02/07/2017

Pubmed ID

28165223

Pubmed Central ID

PMC5332348

DOI

10.1021/acsnano.6b08731

Scopus ID

2-s2.0-85014157600   324 Citations

Abstract

Poor tumor penetration is a major challenge for the use of nanoparticles in anticancer therapy. Moreover, the inability to reach hypoxic tumor cells that are distant from blood vessels results in inadequate exposure to antitumor therapeutics and contributes to development of chemoresistance and increased metastasis. In the present study, we developed iRGD-modified nanoparticles for simultaneous tumor delivery of a photosensitizer indocyanine green (ICG) and hypoxia-activated prodrug tirapazamine (TPZ). The iRGD-modified nanoparticles loaded with ICG and TPZ showed significantly improved penetration in both 3D tumor spheroids in vitro and orthotopic breast tumors in vivo. ICG-mediated photodynamic therapy upon irradiation with a near-IR laser induced hypoxia, which activated antitumor activity of the codelivered TPZ for synergistic cell-killing effect. In vivo studies demonstrated that the nanoparticles could efficiently deliver the drug combination in 4T1 orthotopic tumors. Primary tumor growth and metastasis were effectively inhibited by the iRGD-modified combination nanoparticles with minimal side effects. The results also showed the anticancer benefits of codelivering ICG and TPZ in a single nanoparticle formulation in contrast to a mixture of nanoparticles containing individual drugs. The study demonstrates the benefits of combining tumor-penetrating nanoparticles with hypoxia-activated drug treatment and establishes a delivery platform for PDT and hypoxia-activated chemotherapy.

Author List

Wang Y, Xie Y, Li J, Peng ZH, Sheinin Y, Zhou J, Oupick√Ĺ D

Author

Yuri M. Sheinin MD, PhD Assistant Professor in the Pathology department at Medical College of Wisconsin




MESH terms used to index this publication - Major topics in bold

Animals
Antineoplastic Agents
Apoptosis
Cell Proliferation
Drug Delivery Systems
Drug Screening Assays, Antitumor
Hypoxia
Indocyanine Green
Injections, Intravenous
Mice
Molecular Structure
Nanoparticles
Photochemotherapy
Photosensitizing Agents
Prodrugs
Reactive Oxygen Species
Tissue Distribution
Tumor Cells, Cultured