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Abstract
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In this research, a versatile drug nanocarrier was developed with dual targeting (magnetic and folate receptor) using pH-sensitive Fe3O4/Au core-shell nanomaterials to transport the anticancer drug doxorubicin (Dox). The process involved synthesizing Fe3O4 superparamagnetic nanoparticles (MNPs) as the core, followed by gold coating. A folic acid-functionalized solution was then conjugated to the gold shell via DCC/NHS coupling chemistry and then Dox was loaded onto the nanocarrier. The X-ray diffraction (XRD) analysis showed that the Fe3O4 nanoparticles formed an inverted cubic spinel structure. HRTEM imaging revealed an average particle size of 10 nm, consistent with DLS measurements of 13 nm in solution. VSM measurements at 298 K demonstrated superparamagnetic behavior for both Fe₃O₄ and Fe₃O₄/Au nanoparticles, with saturation magnetization values of 59.46 and 46.67 emu/g, respectively; the reduction of ~21.5% upon Au shell formation is attributed to the magnetic dilution effect of the diamagnetic Au coating, while the retained Ms of 46.67 emu/g remains sufficient for magnetically guided drug delivery. We assessed the compatibility of the lung cancer cell line A549 and the bladder cancer cell line 5637 using an MTT toxicology test. Drug release experiments showed that at pH 5.4, which is typical for cancer cells, 55.95% of Dox was released from the nanocarrier in the first 4 hours, increasing to 68.63% over 93 hours. In contrast, at pH 7.4, typical for healthy cells, 41.24% was released in the first 4 hours, reaching 47.18% after 93 hours. Analysis of drug release kinetics indicated that the release of Dox from this nanocarrier follows a first-order equation. These findings suggest that Dox-loaded Fe₃O₄/Au–FA core-shell nanoparticles hold promise as an effective drug carrier for targeting cancer cells, demonstrating notable cytotoxic activity through selective folate receptor-mediated uptake and pH-responsive sustained release.
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