New method of drug delivery may be safer and more effective against pancreatic cancer

UCLA researchers use nanoparticles to send chemotherapy drug directly to the tumour site, reducing damage to healthy tissues

Huan Meng, Dr Andre Nel and Xiangsheng Liu. Credit: Tunde Akinloye for CNSI

Scientists from the California NanoSystems Institute at UCLA and UCLA’s Jonsson Comprehensive Cancer Centre have developed a delivery system for a chemotherapy drug that greatly reduces side effects while enhancing the drug’s effectiveness against pancreatic cancer. The approach uses mesoporous silica nanoparticles to deliver the drug directly to the tumour instead of having it spread throughout the body via the bloodstream.

The study was led by Dr Andre Nel, Associate Director of the California NanoSystems Institute, and Huan Meng, an assistant professor of nanomedicine; it was published in the journal ACS Nano. Xiangsheng Liu, a postdoctoral scholar in the UC Centre for Environmental Implications of Nanotechnology, was the study’s first author.

In recent years, the chemotherapy regimen known as Folforinox, which combines the drugs 5-fluorouracil, irinotecan, oxaliplatin and leucovorin, has improved survival outcomes over the standard treatment option, gemcitabine, which has fewer side effects. The severe side effects of Folforinox, which are primarily caused by irinotecan, mean that only a minority of the healthiest patients can be treated with it.

Because of stable drug retention by the lipid layers, the nanoparticles greatly reduce the amount of healthy tissue cells exposed to irinotecan

The silica nanoparticles used in the study work like glass bubbles that contain a large amount of irinotecan in pores on their surfaces. The particles are wrapped in a double layer of lipids, similar to cell membranes, which safely trap the drug without leakage until the nanoparticle reaches the cancer site, where it is designed to unload the drug based on the acidic environment of the cancer cell.

'Because of stable drug retention by the lipid layers, the nanoparticles greatly reduce the amount of healthy tissue cells exposed to irinotecan,' Nel said. 'The severe side effects of irinotecan largely result from its exposure to healthy tissues such as bone marrow, liver, and gut.'

The researchers compared the effectiveness of the lipid-coated nanoparticles with an FDA-approved irinotecan carrier that encases drug molecules in fatty spherical particles called liposomes. In mice with human pancreatic tumours, delivering the drug via silica nanoparticles reduced tumour size more effectively than delivering it via liposomes. The nanoparticle technique was also safer because less of the drug leaked into the bloodstream.

The researchers believe that a Folforinox regimen could be made safer and more effective against pancreatic cancer using the mesoporous silica nanoparticle delivery system for irinotecan.

Meng said they still have a way to go before launching a human clinical trial, but with this study they have developed a normal strategy for irinotecan delivery by a nanoparticle.

The researchers also found that their approach can be used to deliver several other chemotherapy drugs, meaning that it may also prove useful in treating other types of cancer.