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

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.

Nanoparticle-Based Drug Delivery in Cancer Therapy and Its Role in Overcoming Drug Resistance

“…Compared to unmodified NPs, transferrin-modified NPs have been shown to exhibit higher cellular uptake efficiency and enhanced intracellular delivery of drugs ( Cui et al, 2017 ). Moreover, evidence indicates that transferrin-conjugated polymeric NPs play a significant role in overcoming drug-resistant chemotherapy ( Soe et al, 2019 ).…”

Cancer Nanopharmaceuticals: Physicochemical Characterization and In Vitro/In Vivo Applications

“…Such formed nanoparticles were evaluated in vivo and confirmed pronounced inhibition of tumor growth in mice using the Dalton Lymphoma ascites (DLA) model. Soe et al (2019) demonstrated on the other hand how one can improve the DOX delivery via utilization of the polymeric nanoparticles for the Doxorubicin-Resistant breast cancer cells [ 153 ].…”

Surface‐functionalised hybrid nanoparticles for targeted treatment of cancer

“…The intracellular accumulation of drugs in a robust tumour environment increases with passive targeting strategy and this is achieved through increased permeability and retention effect. Actively guided NPs have beneficial effects on chemotherapeutic drug delivery mechanisms such as enhancing drug persistence in cancer cells by improving cell attachment, drug accumulation, and increase uptake by cancer cells through receptor‐mediated endocytosis [14]. Metallic NPs are used in photothermal therapy (PTT) and showed excellent results in vivo by thermal ablation of the tumour (Fig.…”

“…Doxorubicin (DOX) is one of the most effective chemotherapeutic agents used in the treatment of many cancers, such as breast and ovarian cancer. It can kill cancer cells directly by DNA damage or by elevated ROS and thus inducing apoptosis in the tumour cells [14, 78]. To combat MDR in the treatment of cancer, a current study described the development of transferrin (Tf)‐conjugated polymeric NP for the targeted delivery of DOX.…”

“…To combat MDR in the treatment of cancer, a current study described the development of transferrin (Tf)‐conjugated polymeric NP for the targeted delivery of DOX. The results showed that in DOX‐resistant (R) breast cancer cell lines, the NPs provided substantial antitumour efficiency with minimal toxicity to normal cells [14]. Similarly, another study revealed the development of magnesium oxide (MgO) nanoflakes as drug transporters and loaded them with DOX for simultaneous treatment of cancer and hypomagnesemia.…”