The Biological Properties and Cancer Therapeutic Applications of Artificially Synthesized Gold Nanoparticles with Surface Modifications
Date Issued
2009
Date
2009
Author(s)
Wu, Ching-Ming
Abstract
Gold nanoparticles (AuNPs) with its distinctive physical and chemical properties and well as biocompatibility have been utilized in the fields of photoacoustic imaging, delivery of genes and laser induced photothermal therapy in recent years. In this study, we fabricated two types of gold-nanoparticles with various surface modifications. Their biological properties and potential biomedical applications were explored. In the in vitro biocompatibility evaluation, those PEG modified nanoparticles exhibit better compatibility in the MTT assays. The in vivo biodistribution analysis was performed using BALB/c mice through I.V. injection via tail vein followed by Atomic Absorption Spectroscopy analysis. We discovered that most nanoparticles accumulated in the spleen and liver, and few of them were found in heart, lung and kidney. The nanoparticles were then excreted via kidney and gastrointestinal tract and can be detected in urine and feces 24 hr after injection. The conformation, size and surface modifications all contribute to their in vivo biodistribution. Together with the results from biocompatibility, biodegradation and biodistribution will contribute to our understanding of the pharmacokinetic and toxicity of nanoparticles and to develop better nano carrier.o evaluate the chemotherapeutic efficiency of our AuNPs, oligonucleotide conjugated AuNPs was applied as the carrier for simultaneous DNA and anti-cancer nucleoside delivery. The polynucleotide was modified with thiol group in the 5’ end. Under a salt gradient, these oligonucleotides form high-density self-assembled monolayer on the particle surface. The nanoparticle-oligonucleotide complex presented higher capacity in carrying 5-FU anti-cancer compounds than the original gold particles. The hydrodynamic size of the AuNPs increased from 25 to 35nm with an increase in the negative surface charge from -9.58 to -21.66mV after polynucleotide conjugation and drug loading. A positive association between environmental pH and the drug release was observed in PBS, which implied their potential use in the controlled localized drug release in the lower GI tract. The MTT assay revealed a dose dependent cytotoxicity of the nanoparticle- oligonucleotide-anti-cancer drug complex to colon cancer cell line than the free compounds of the same dosage. This new polynucleotide-AuNPs complex presented great potential to be used as the environmental controlled anti-cancer nanocapsule, especially for per oral colon cancer chemotherapy. As gold nanoparticles have been shown to be a good photoacoustic imaging contrast agent, their potential as an excellent nano vehicles for combined molecular imaging and cancer drug are highly expected.
Subjects
gold nanoparticles
drug carrier
nucleoside
cancer
SDGs
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