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ACS Appl Mater Interfaces. 2019 Jul 10;11(27):23909-23918. doi: 10.1021/acsami.9b07483. Epub 2019 Jun 25.

Tumor Homing Reactive Oxygen Species Nanoparticle for Enhanced Cancer Therapy.

Author information

1
Department of Chemistry and Chemical Biology , Rutgers, The State University of New Jersey , Piscataway , New Jersey 08854 , United States.
2
Department of Chemical & Biomolecular Engineering , Sogang University , Seoul 04107 , Republic of Korea.
3
Department of Nanobiotechnology , Atatürk University , Erzurum 25030 , Turkey.
4
Department of Biological Sciences, Laboratory of Stem Cell Research and Biotechnology , Hyupsung University , Hwasung-si 18330 , Republic of Korea.
5
Department of Biotechnology, Laboratory of Stem Cells and Tissue Regeneration, College of Life Sciences and Biotechnology , Korea University , Seoul 02841 , Republic of Korea.
6
School of Integrative Engineering , Chung-Ang University , Seoul 06974 , Republic of Korea.
7
Department of Life and Nanopharmaceutical Science, College of Pharmacy , Kyung Hee University , Seoul 02447 , Republic of Korea.

Abstract

Multifunctional nanoparticles that carry chemotherapeutic agents can be innovative anticancer therapeutic options owing to their tumor-targeting ability and high drug-loading capacity. However, the nonspecific release of toxic DNA-intercalating anticancer drugs from the nanoparticles has significant side effects on healthy cells surrounding the tumors. Herein, we report a tumor homing reactive oxygen species nanoparticle (THoR-NP) platform that is highly effective and selective for ablating malignant tumors. Sodium nitroprusside (SNP) and diethyldithiocarbamate (DDC) were selected as an exogenous reactive oxygen species (ROS) generator and a superoxide dismutase 1 inhibitor, respectively. DDC-loaded THoR-NP, in combination with SNP treatment, eliminated multiple cancer cell lines effectively by the generation of peroxynitrite in the cells (>95% cell death), as compared to control drug treatments of the same concentration of DDC or SNP alone (0% cell death). Moreover, the magnetic core (ZnFe2O4) of the THoR-NP can specifically ablate tumor cells (breast cancer cells) via magnetic hyperthermia, in conjunction with DDC, even in the absence of any exogenous RS supplements. Finally, by incorporating iRGD peptide moieties in the THoR-NP, integrin-enriched cancer cells (malignant tumors, MDA-MB-231) were effectively and selectively killed, as opposed to nonmetastatic tumors (MCF-7), as confirmed in a mouse xenograft model. Hence, our strategy of using nanoparticles embedded with ROS-scavenger-inhibitor with an exogenous ROS supplement is highly selective and effective cancer therapy.

KEYWORDS:

cancer therapy; magnetic core−shell nanoparticles; nanotechnology; reactive species; tumor targeting

PMID:
31252451
DOI:
10.1021/acsami.9b07483
[Indexed for MEDLINE]

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