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

• Main Authors: Zar Chi Soe, Jun Bum Kwon, Raj Kumar Thapa, Wenquan Ou, Hanh Thuy Nguyen, Milan Gautam, Kyung Taek Oh, Han-Gon Choi, Sae Kwang Ku, Chul Soon Yong, Jong Oh Kim
• Format: Article
• Language: English
• Published: MDPI AG 2019-02-01
• Series: Pharmaceutics
• Subjects: doxorubicin; doxorubicin-resistant cancer; polymeric nanoparticles; transferrin
• Online Access: https://www.mdpi.com/1999-4923/11/2/63

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<i>&amp;</i>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<i>&amp;</i>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<i>&amp;</i>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<i>&amp;</i>P123-T_f has been tailored, using the principles of nanotherapeutics, to overcome drug-resistant chemotherapy.