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

Pharmaceutics

SaeKwang Ku¹  KyungTaek Oh²  Han-Gon Choi³  ChulSoon Yong⁴  HanhThuy Nguyen⁴  Wenquan Ou⁴  Milan Gautam⁴  ZarChi Soe⁴  RajKumar Thapa⁴  JongOh Kim⁴  JunBum Kwon⁴ 

[1] College of Korean Medicine, Daegu Haany University, Gyeongsan 712-715, Korea;College of Pharmacy, Chung-Ang University, 221 Heuksuk-dong Dongjak-gu, Seoul 156-756, Korea;College of Pharmacy, Institute of Pharmaceutical Science and Technology, Hanyang University, 55 Hanyangdaehak-ro, Sangnok-gu, Ansan 426-791, Korea;College of Pharmacy, Yeungnam University, 214-1, Dae-dong, Gyeongsan 712-749, Korea;

关键词: doxorubicin;    doxorubicin-resistant cancer;    polymeric nanoparticles;    transferrin;   

DOI  :  10.3390/pharmaceutics11020063

来源: DOAJ

【 摘 要 】

In this study, a transferrin (T_f)-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 (T_f)-conjugated polymeric nanoparticle composed of poloxamer 407 (F127) and 123 (P123) (Dox/F127&P123-T_f), 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-T_f 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-T_f 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-T_f has been tailored, using the principles of nanotherapeutics, to overcome drug-resistant chemotherapy.

【 授权许可】

Unknown