Folic Acid-Functionalized, Condensed Magnetic Nanoparticles for Targeted Delivery of Doxorubicin to Tumor Cancer Cells Overexpressing the Folate Receptor

Abstract

This study concerns the development of folic acid (FA)-functionalized iron oxide condensed colloidal magnetic clusters for a more selective delivery of doxorubicin (DOX) to tumor cancer cells overexpressing the folate receptor. Alginate-coated condensed magnetic nanoparticles (co-MIONs) were synthesized via an alkaline precipitation method of an iron precursor in the presence of sodium alginate. Poly(ethylene glycol) (OH-PEG-NH2) was conjugated to the carboxylic acid end group of alginate and folic acid (FA) was conjugated to the hydroxyl terminal group of PEG to produce folate-functionalized, pegylated co-MIONS (Mag-Alg-PEG-FA). The physicochemical properties of nanoparticles were fully characterized. DOX was loaded on the nanoparticles, and the cellular uptake and anticancer efficacy of the nanoparticles were examined in cancer cell lines expressing and not expressing the folate receptor. The biocompatibility of the carrier (blank nanoparticles) was also evaluated by cytocompatibility and hemocompatibility experiments. The nanoparticles exhibited sustained DOX release in aqueous buffers and biorelevant media, which was responsive to pH and external alternating current magnetic fields. The effect of the magnetic field on DOX percentage release appeared to be independent of the timing (onset time) of magnetic field application, providing flexibility to the magnetic control of drug release from the nanoparticles. The blank nanoparticles were not cytotoxic and did not cause hemolysis. The DOX-loaded and FA-functionalized nanoparticles exhibited increased uptake and caused increased apoptosis and cytotoxicity against the MDA-MB-231 cell line, expressing the folate receptor, compared to the MCF-7 cell line, not expressing the folate receptor. The application of a 0.5 T magnetic field during incubation of the nanoparticles with the cancer cells increased the cellular uptake and cytotoxicity of the nanoparticles. The obtained results indicate the potential of the folate-functionalized, pegylated co-MIONS for a more efficacious DOX delivery to cancer cells of solid tumors.

Design and Synthesis of Multi-Functional Superparamagnetic Core-Gold Shell Nanoparticles Coated with Chitosan and Folate for Targeted Antitumor Therapy

“…DOX-loaded FA-CS-SPION@Au NPs had a size particle average of 102.6 ± 7 nm. Encapsulation was performed under the electrostatic load capacity of DOX to SPION@Au-CS-FA NPs by using the electrostatic interaction between the carboxyl group of carboxylic acid-functional iron-oxide NPs and the DOX amine group [ 32 ].…”

Shortwave Infrared-Emitting Theranostics for Breast Cancer Therapy Response Monitoring

“…The concentration of Dox in the supernatant was calculated against a Dox standard curve. The loading efficiency (LE) of Dox was assessed based on the fluorescence of unloaded Dox in the supernatant ( Janes et al, 2001 ; Andhariya et al, 2010 ; Qi et al, 2010 ; Nigam et al, 2011 ; Abbasi et al, 2012 ; Park et al, 2012 ; Unsoy et al, 2014 ; Angelopoulou et al, 2019 ) using the equation:…”

Self-assembled polymeric nanocarrier-mediated co-delivery of metformin and doxorubicin for melanoma therapy

“…Last but not least, to achieve specific targeting efficiency, molecular targeting agents, such as antibodies, peptides, and folic acid, have been grafted onto nanodrug delivery systems (Liu et al., 2019 ). Among which, folic acid is an essential component in DNA synthesis, repair, and methylation, as well as amino acid and RNA metabolism, and plays a vital role in cell growth and division (Angelopoulou et al., 2019 ). Given that cancer cells, including melanoma cells, express high levels of folate receptors, and utilize more folate than normal cells to maintain their uncontrollable growth (Musalli et al., 2020 ), the folic acid/folate receptor axis is considered as a molecular target for cancer treatment.…”