Folic acid-modified methotrexate-conjugated gold nanoparticles as nano-sized trojans for drug delivery to folate receptor-positive cancer cells.

Methotrexate (MTX), an analog of folic acid (FA), is a drug widely used in cancer treatment. To prevent its potential toxicity and enhance therapeutic efficacy, targeted drug delivery systems, especially nanotechnology-folate platforms, are a central strategy. Gold nanoparticles (AuNPs) are promising candidates to be used as drug delivery systems because of their small particle sizes and their inertness for the body. In this study, glutathione (GSH)-coated FA-modified spherical AuNPs (5.6 nm) were successfully synthesized, and the anticancer activity of novel MTX-loaded (MTX/Au-GSH-FA) NPs (11 nm) was examined. Dynamic light scattering (DLS) and transmission electron microscopy (TEM) results showed that MTX/AuNPs possess spherical morphology, nanoscaled particle size, narrow size distribution, and good stability. In vitro studies showed that cytotoxicity of MTX/Au-GSH-FA to folate receptor-positive (FR+) human brain (U-87 MG) and cervical (HeLa) cancer cells enhanced significantly (∼3 and ∼10 fold, respectively) compared to free MTX while there was no significant effect in FR-negative human cell lines A549 (lung carcinoma), PC3 (prostate carcinoma), HEK-293 (healthy embryonic kidney). Moreover, the receptor specificity of the conjugate was shown by fluorescent microscopic imaging. In conclusion, these results indicate that the synthesized novel MTX/Au-GSH-FA NP complex seems to be a good candidate for effective and targeted delivery in FR+ cancer therapy.

Design of an amphiphilic hyperbranched core/shell-type polymeric nanocarrier platform for drug delivery.

An amphiphilic core/shell-type polymer-based drug carrier system (HPAE- PCL-b -MPEG), composed of hyperbranched poly(aminoester)-based polymer (HPAE) as the core building block and poly(ethylene glycol)-b - poly(ε-caprolactone) diblock polymers (MPEG-b -PCL) as the shell building block, was designed. The synthesized polymers were characterized with FTIR, 1 H NMR, 13 C NMR, and GPC analysis. Monodisperse HPAE-PCL-b - MPEG nanoparticles with dimensions of < 200 nm and polydispersity index of < 0.5 were prepared by nanoprecipitation method and characterized with SEM, particle size, and zeta potential analysis. 5-Fluorouracil was encapsulated within HPAE-PCL-b -MPEG nanoparticles. In vitro drug release profiles and cytotoxicity of blank and 5-fluorouracil-loaded nanoparticles were examined against the human colon cancer HCT116 cell line. All results suggest that HPAE-PCL-b - MPEG nanoparticles offer an alternative and effective drug nanocarrier system for drug delivery applications.