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Pharmaceutics. 2019 Feb 1;11(2). pii: E63. doi: 10.3390/pharmaceutics11020063.

Transferrin-Conjugated Polymeric Nanoparticle for Receptor-Mediated Delivery of Doxorubicin in Doxorubicin-Resistant Breast Cancer Cells.

Author information

1
College of Pharmacy, Yeungnam University, 214-1, Dae-dong, Gyeongsan 712-749, Korea. zarchisoeygn96@gmail.com.
2
Department of Pharmaceutics, University of Pharmacy (Yangon), Waybargi Road, North Okkalapa township, Yangon 11031, Myanmar. zarchisoeygn96@gmail.com.
3
College of Pharmacy, Yeungnam University, 214-1, Dae-dong, Gyeongsan 712-749, Korea. kgb0703@hanmail.net.
4
College of Pharmacy, Yeungnam University, 214-1, Dae-dong, Gyeongsan 712-749, Korea. thapa.rajkumar7@gmail.com.
5
College of Pharmacy, Yeungnam University, 214-1, Dae-dong, Gyeongsan 712-749, Korea. owqcn@foxmail.com.
6
College of Pharmacy, Yeungnam University, 214-1, Dae-dong, Gyeongsan 712-749, Korea. nguyenhanhthuy.87@gmail.com.
7
College of Pharmacy, Yeungnam University, 214-1, Dae-dong, Gyeongsan 712-749, Korea. gtmmilan2@gmail.com.
8
College of Pharmacy, Chung-Ang University, 221 Heuksuk-dong Dongjak-gu, Seoul 156-756, Korea. kyungoh@cau.ac.kr.
9
College of Pharmacy, Institute of Pharmaceutical Science and Technology, Hanyang University, 55 Hanyangdaehak-ro, Sangnok-gu, Ansan 426-791, Korea. hangon@hanyang.ac.kr.
10
College of Korean Medicine, Daegu Haany University, Gyeongsan 712-715, Korea. gucci200@hanmail.net.
11
College of Pharmacy, Yeungnam University, 214-1, Dae-dong, Gyeongsan 712-749, Korea. csyong@yu.ac.kr.
12
College of Pharmacy, Yeungnam University, 214-1, Dae-dong, Gyeongsan 712-749, Korea. jongohkim@yu.ac.kr.

Abstract

In this study, a transferrin (Tf)-conjugated polymeric nanoparticle was developed for the targeted delivery of the chemotherapeutic agent doxorubicin (Dox) in order to overcome multi-drug resistance in cancer treatment. Our objective was to improve Dox delivery for producing significant antitumor efficacy in Dox-resistant (R) breast cancer cell lines with minimum toxicity to healthy cells. The results of our experiments revealed that Dox was successfully loaded inside a transferrin (Tf)-conjugated polymeric nanoparticle composed of poloxamer 407 (F127) and 123 (P123) (Dox/F127&P123-Tf), which produced nanosized particles (~90 nm) with a low polydispersity index (~0.23). The accelerated and controlled release profiles of Dox from the nanoparticles were characterized in acidic and physiological pH and Dox/F127&P123-Tf enhanced Dox cytotoxicity in OVCAR-3, MDA-MB-231, and MDA-MB-231(R) cell lines through induction of cellular apoptosis. Moreover, Dox/F127&P123-Tf inhibited cell migration and altered the cell cycle patterns of different cancer cells. In vivo study in MDA-MB-231(R) tumor-bearing mice demonstrated enhanced delivery of nanoparticles to the tumor site when coated in a targeting moiety. Therefore, Dox/F127&P123-Tf has been tailored, using the principles of nanotherapeutics, to overcome drug-resistant chemotherapy.

KEYWORDS:

doxorubicin; doxorubicin-resistant cancer; polymeric nanoparticles; transferrin

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