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Open AccessArticle

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

1
College of Pharmacy, Yeungnam University, 214-1, Dae-dong, Gyeongsan 712-749, Korea
2
Department of Pharmaceutics, University of Pharmacy (Yangon), Waybargi Road, North Okkalapa township, Yangon 11031, Myanmar
3
College of Pharmacy, Chung-Ang University, 221 Heuksuk-dong Dongjak-gu, Seoul 156-756, Korea
4
College of Pharmacy, Institute of Pharmaceutical Science and Technology, Hanyang University, 55 Hanyangdaehak-ro, Sangnok-gu, Ansan 426-791, Korea
5
College of Korean Medicine, Daegu Haany University, Gyeongsan 712-715, Korea
*
Authors to whom correspondence should be addressed.
These authors contributed equally to this work.
Pharmaceutics 2019, 11(2), 63; https://doi.org/10.3390/pharmaceutics11020063
Received: 31 December 2018 / Revised: 23 January 2019 / Accepted: 30 January 2019 / Published: 1 February 2019
(This article belongs to the Special Issue Advanced Formulation Approaches for Targeted Drug Delivery)
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. View Full-Text
Keywords: doxorubicin; doxorubicin-resistant cancer; polymeric nanoparticles; transferrin doxorubicin; doxorubicin-resistant cancer; polymeric nanoparticles; transferrin
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Soe, Z.C.; Kwon, J.B.; Thapa, R.K.; Ou, W.; Nguyen, H.T.; Gautam, M.; Oh, K.T.; Choi, H.-G.; Ku, S.K.; Yong, C.S.; Kim, J.O. Transferrin-Conjugated Polymeric Nanoparticle for Receptor-Mediated Delivery of Doxorubicin in Doxorubicin-Resistant Breast Cancer Cells. Pharmaceutics 2019, 11, 63.

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