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

다국어 초록 (Multilingual Abstract)

<P><B>Abstract</B></P> <P>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<SUP>®</SUP>, while its cellular uptake was higher than that of Doxil<SUP>®</SUP>. Thus, this novel receptor-based TfS NP drug delivery system has great potential to target TfR-overexpressing cancer cells without off-target effects.</P> <P><B>Highlights</B></P> <P> <UL> <LI> Apo-transferrin and stearic acid conjugate could form self-assembled NP. </LI> <LI> Apo-transferrin and stearic acid were used as a NP core. </LI> <LI> Drug-loaded NPs showed superior cancer cell targeting and killing efficiency. </LI> <LI> The prepared NPs were as comparable as the PEGylated liposomal product, Doxil<SUP>®</SUP>. </LI> <LI> The NP system has potential to deliver both hydrophilic and hydrophobic drug. </LI> </UL> </P> <P><B>Graphical abstract</B></P> <P>Mechanistic pathway of prepared TfS NPs for cellular uptake and trafficking in transferrin receptor over-expressing cancer cells.</P> <P>[DISPLAY OMISSION]</P>