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Engineered Nano-delivery of Gemcitabine for Pancreatic Cancer (in Mice)

Normally, we do not address pre-clinical studies for pancreatic cancer (ductal adenocarcinoma of the pancreas) in the Pancreatica Blog as so many of these fail when finally subjected to human testing. But sometimes there are such studies that are so intriguing that they cannot be easily ignored. And this particular research study of nanotherapy for the treatment of pancreatic cancer is one of them. And it ties in with another recent of our Blog articles.

Nanotechnology in this context is a term that refers to applying designed miniaturized technology to the “molecular” level of a biological system.

In this current study Nel and his colleagues at UCLA created a two-stage nano system designed to help defeat the substantive stromal protection of adenocarcinoma of the pancreas, thereby delivering a higher concentration of chemotherapy to the pancreatic tumor.  Their work was published in the November 26th 2013 issue of the journal ACS Nano, a publication not of the American Cancer Society – but of the American Chemical Society.

The first step is that the researchers developed a PEGylated liposome to carry gemcitabine to the actual pancreatic cancer tumor body – the liposome here is a bubble-like structure involving polyethylene glycol as a carry and releasing agent.  These structures proved too large to easily penetrate the pancreatic tumor stromal tissue. So, the researchers next found a way to confound the TGF-β (Transforming Growth Factor beta) signaling pathway – which helps regulate the size and integrity of tumor vascular fenestrations involving the stroma.  This was accomplished through applying a complex created by the marriage of polyethylene glycol (PEG)-coated mesoporous silica nanoparticles together with the known TGF-β inhibitor, LY364947. This effectively enlarged the fenestrations such that now the liposomes were able to relatively freely penetrate the pancreatic cancer stromal tissue.

The system was subsequently employed in mice – resulting in effects that demonstrated faster and more adenocarcinoma tumor-concentrated (efficient) gemcitabine levels, reduced apparent systemic toxicity of gemcitabine (by murine body weight, blood chemistry, and histology), and most importantly a rather dramatic reduction of the pancreatic cancer tumor burden (as determined by tumor weight) which effect especially became increasingly significant beginning at about day 25 of the treatment regimen.

This is a most interesting study.  It speaks to the problem of stroma – one of the known obstacles for chemotherapy in pancreatic cancer.  Additionally, this kind of approach would presumably be more intrinsically efficient and reduce the attendant side-effects of the chemotherapy.  There will likely for now be more pre-clinical studies.  And one day, perhaps early clinical trials?


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Dale O’Brien, MD