Targeted Ultrafine Iron Oxide Nanoparticles for Delivery of the Topoisomerase Inhibitor SN38 and Ovarian Cancer Treatment

Author:

Liu Nianyuan1,Lai Lanjin2,Xu Peijia1,Padelford Jonathan3,Xue Ting1,Zhang Hua4,Zhu Xingkai5,Xue Xingkui1,Wang Liya1

Affiliation:

1. Radiology, Affiliated Longhua People’s Hospital, The Third School of Clinical Medicine, Southern Medical University, Shenzhen, 518109, CN

2. Radiology, Shenzhen Hospital of Guangzhou University of Chinese Medicine, Shenzhen, 518034, China

3. 5M Biomed, Limited Liability Company, Atlanta, Georgia, 30333, USA

4. Radiology, The First Hospital of Nanchang, Nanchang, 330008, China

5. School of Public Health, Guangdong Medical University, Dongguan, 523808, China

Abstract

Ovarian cancer remains a challenge to decrease mortality and improve diagnostic efficiency in gynecological cancers. To develop a delivery system capable of efficient cancer cell targeting and delivering novel efficacious therapeutics, we assembled folic acid (FA) conjugated ultrafine iron oxide nanoparticles (uIONP) with encapsulation of DNA topoisomerase inhibitor SN38, which target ovarian cancer cells with over-expression of folate receptor alpha (FRα) and deliver SN38 to induce apoptosis. The assembled FA-uIONP-SN38 exhibited higher drug loading efficiency than the larger counterparts with core diameters more than 10 nm. The targeting specificity of FA-uIONP-SN38 for SKOV-3 cancer cells was validated, with HEK293 kidney cells and Raw264.7 macrophages as non-targeted cell line control. It was found that more SKOV-3 cancer cells were killed due to apoptosis by FA-uIONP-SN38 at the same SN38 dosages compared with uIONP-SN38 and free SN38, respectively. The delivery of this inhibitor to SKOV-3 cancer cells by FRα-targeted FA-uIONP carrier was enhanced by about 10-folds with less cytotoxicity comparing to the free drug SN38. The developed FA-uIONP-SN38 holds a great potential as a theranostic approach in treating ovarian cancer.

Publisher

American Scientific Publishers

Subject

General Medicine

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