Fattigation-platform nanoparticles using apo-transferrin stearic acid as a core for receptor-oriented cancer targeting

• Published in: Colloids and surfaces, B, Biointerfaces B, Biointerfaces, 2017-11, Vol.159, p.571-579
• Main Authors: Amin, Hardik H., Meghani, Nilesh M., Park, Chulhun, Nguyen, Van Hong, Tran, Thao Truong-Dinh, Tran, Phuong Ha-Lien, Lee, Beom-Jin
• Format: Article
• Language: English
• Subjects: Apo-transferrin-stearic acid conjugate; Doxorubicin; Fattigation-platform; Physicochemical characterization; Receptor-oriented cancer targeting; Self-assembled nanoparticles; Transferrin
• ISSN: 0927-7765; 1873-4367
• DOI: 10.1016/j.colsurfb.2017.08.014

Mechanistic pathway of prepared TfS NPs for cellular uptake and trafficking in transferrin receptor over-expressing cancer cells. [Display omitted] •Apo-transferrin and stearic acid conjugate could form self-assembled NP.•Apo-transferrin and stearic acid were used as a NP core.•Drug-loaded NPs showed superior cancer cell targeting and killing efficiency.•The prepared NPs were as comparable as the PEGylated liposomal product, Doxil®.•The NP system has potential to deliver both hydrophilic and hydrophobic drug. A major hurdle in cancer treatment is the precise targeting of drugs to the cancer site. As many cancer cells overexpress the transferrin receptor (TfR), the transferrin (Tf)-TfR interaction is widely exploited to target cancer cells. In this study, novel amphiphilic apo-Tf stearic acid (TfS) conjugates were prepared and characterized by Fourier transform infrared (FTIR) spectroscopy, matrix-assisted laser desorption/ionization-time of flight (MALDI-TOF) mass spectrometry, and trinitrobenzenesulfonic acid (TNBS) assay. The prepared TfS conjugates were readily self-assembled in water to form nanoparticles (NPs), consisting of TfS as a core of NPs, whose sizes and zeta potentials were determined by scanning electron microscopy (SEM), transmission electron microscopy (TEM), and a particle size analyzer. Hydrophilic water-soluble doxorubicin (DOX) was chosen as a model drug. DOX-loaded TfS NPs (NP+DOX), prepared by the adsorption of DOX on the NP surface via the incubation method, were analyzed for their cell targeting and killing efficiencies in TfR-overexpressing A549 and HCT116 cell lines by MTT assay, confocal microscopy, and fluorescence assisted cell sorting (flow cytometry). The data showed that NP+DOX exhibited improved cancer cell targeting and killing properties compared to that reported for free DOX. Further, the cytotoxic efficiency of NP+DOX was comparable to that of PEGylated liposomal product, Doxil®, while its cellular uptake was higher than that of Doxil®. Thus, this novel receptor-based TfS NP drug delivery system has great potential to target TfR-overexpressing cancer cells without off-target effects.