Abstract
We report a comparative study of synthesis, characteristics and in vitro tests of two folate-conjugated gold nanoparticles (AuNP) differing in linkers and AuNP sizes for selective targeting of folate-receptor positive cancerous cells. The linkers chosen were 4-aminothiophenol (4Atp) and 6-mercapto-1-hexanol (MH) with nanoconjugate products named Folate-4Atp-AuNP and Folate-MH-AuNP. We report the folate-receptor tissue distribution and its endocytosis for targeted nanotechnology. Comparison of the two nanoconjugates’ syntheses and characterization is also reported, including materials and methods of synthesis, UV-visible absorption spectroscopic measurements, Fourier Transform Infra Red (FTIR) measurements, Transmission electron microscopy (TEM) images and size distributions, X-ray diffraction data, elemental analyses and chemical stability comparison. In addition to the analytical characterization of the nanoconjugates, the cell lethality was measured in HeLa (high level of folate receptor expression) and MCF-7 (low level of folate receptor expression) cells. The nanoconjugates themselves, as well as the intense pulsed light (IPL) were not harmful to cell viability. However, upon stimulation of the folate targeted nanoconjugates with the IPL, ~98% cell killing was found in HeLa cells and only ~9% in MCF-7 cells after four hours incubation with the nanoconjugate. This demonstrates that folate targeting is effective in selecting for specific cell populations. Considering the various comparisons made, we conclude that Folate-4Atp-AuNP is superior to Folate-MH-AuNP for cancer therapy.
Highlights
Background and IntroductionA need exists to target cancer treatments to the tumor site, without damaging healthy tissue
The reagent grade chemical and biological compounds that are used in this research are as follows: Hydrogen tetrachloroaurate (III) trihydrate (HAuCl4.3H2O), 4-aminothiophenol (C6H7NS), 6-mercapto1-hexanol (C6H14OS), Sodium borohydride (NaBH4), N, N'-dicyclohexylcarbodiimide (C13H22N2), Folic acid (C19H19N7O6), Trypan blue, RPMI 1640, MTT (3-[4,5-dimethylthiazol-2-yl]-2,5diphenyltetrazoliumbromide), dimethylsulfoxide (DMSO), streptomycin, penicillin and trypsin-EDTA, Fetal calf serum (FCS), and HeLa and MCF7 cell lines
We have investigated the differences between using the nanoconjugates along with intense pulsed light (IPL) exposure for the HeLa cell line, which is folate-receptor overexpressing and the MCF7 cell line, which expresses a low level of folate-receptors
Summary
A need exists to target cancer treatments to the tumor site, without damaging healthy tissue. Nanotechnology offers the potential to selectively seek out and destroy cancerous tissues by a variety of targeting and destruction methods. A malignant cancer is typically fast growing, which means that it requires more nutrients and increased waste removal than healthy tissues. The residence time within the tumor is limited due to random diffusion into and out of the tumor. Increasing the residence time of nanotechnology-based cancer treatments within tumors is necessary. To achieve increased residence time, active targeting must be used. Active targeting is based on selectively targeting cancer cells through a specific binding site on the surface of the cell, such as a receptor
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