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Friday, 16 November 2012

Gold nanoparticles may enable safer chemotherapy

Publishing in PLOS One, ICREA Research Professor Leader Victor Puntes and colleagues report safe and effective gold-nanoparticle delivery of cisplatin in mouse models of cancer.

Continuing on their previous advances in this project, the team offers detailed information on the safety, efficacy and fate of gold nanoparticle conjugates of cisplatin administered to mice with tumours, including their distribution in and effects on different body tissues.

Professor Victor Puntes, who leads ICN’s Inorganic Nanoparticles Group, and colleagues from various centres in Spain have just published an article in the journal PLOS One describing their latest findings on the efficacy and safety of custom-designed gold nanoparticles as drug-delivery vehicles for the chemotherapeutic agent cisplatin. The team reports that in mouse models of cancer, their gold nanoparticle/cisplatin system is markedly less toxic than free cisplatin, but just as effective.Exploiting the size and surface chemistry of gold nanoparticles, the team has developed a conjugate drug delivery system in which cisplatin molecules are bound to gold nanoparticles. This protects the drug against deactivation by plasma proteins, and enables its selective release in the body through pH-sensitive chemistry. Following the design and synthesis of the conjugate, the team first compared their conjugate to free cisplatin for efficacy in human lung cancer cells (line A549). To guage therapeutic efficacy, they assessed the speed at which the cells took up the drug and measured the cellular DNA levels of the drug at different time points. The cells treated with the conjugate took it up faster than the cells treated with the free drug took that up, and after 24 hours of cellular incubation, the DNA levels of the drug in the conjugate-treated cells were 125 times higher than those in the free-drug-treated cells. They then explored the mechanistic details of uptake in each case.The researchers then assessed the overall efficacy of this system compared to freely-administered cisplatin in mouse models of cancer, they team was also able to temporally track the nanoparticles (by tracking gold) and the drug (by tracking platinum) inside the animals. This enabled them to quantify, the accumulation of the nanoparticles in the tumour, the blood and in different organs (heart, lungs, kidney, brain, liver, spleen and ovaries). They found that animals treated with the conjugate had five to ten times lower brain levels of platinum than did those treated with the free drug, and that with the exception of the liver and spleen, the levels were consistently lower in the organs of the conjugate-treated animals. They correlated these differences in biodistribution to the markedly lower levels of toxicity observed in the conjugate-treated mice.To read the full article, “Detoxifying Antitumoral Drugs via Nanoconjugation: The Case of Gold Nanoparticles and Cisplatin”, click here.