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Liposomes, the first type of nanoparticle to achieve clinical use, are remarkably versatile constructs, but they suffer from a general lack of stability. But researchers at the Nanomaterials for Cancer Diagnostics and Therapeutics Center for Cancer Nanotechnology Excellence at Northwestern University have developed a method for stabilizing liposomes within a polymer cage. More importantly, the polymer cage is constructed to fall apart and trigger drug release from the liposome when taken into cells.
Reporting its work in the Journal of the American Chemical Society, a research team led by Thomas O'Halloran, Ph.D., and SonBinh Nguyen, Ph.D., showed that a cholesterol-poly(acrylic acid) construct could be inserted into the outer membrane of a liposome and then crosslinked with the poly(acrylic acid) chains to form what is essentially a cage surrounding the liposome. The resulting polymer-caged liposomes are stable, both in serum and during freeze-drying and rehydration. This latter observation is a promising observation for future commercial production and shelf-life concerns. In contrast, freeze-drying and rehydration destroy conventional liposomes. In one assay, the investigators found that only about 5 percent of the liposome's payload leaked out of the formulation over the course of 500 hours.
Of course, a permanently stable construct that would not release its contents would not serve well as a drug delivery vehicle, but this particular polymer cage is unstable at the pH found inside tumor cells. Indeed, when incubated at pH 4, the polymer-caged liposomes released 84 percent of their payload over 150 hours. The researchers note that their process should work with any liposome and that the polymer cage can also serve as a ready point of attachment for targeting ligands.
This work, which was supported in part by the National Cancer Institute's Alliance for Nanotechnology in Cancer, is detailed in the paper "Polymer-caged liposomes: pH-responsive delivery system with high stability." This paper was published online in advance of print publication. An abstract of this paper is available through PubMed.
About National Cancer Institute
To help meet the goal of reducing the burden of cancer, the National Cancer Institute (NCI), part of the National Institutes of Health, is engaged in efforts to harness the power of nanotechnology to radically change the way we diagnose, treat and prevent cancer.
The NCI Alliance for Nanotechnology in Cancer is a comprehensive, systematized initiative encompassing the public and private sectors, designed to accelerate the application of the best capabilities of nanotechnology to cancer.
Currently, scientists are limited in their ability to turn promising molecular discoveries into benefits for cancer patients. Nanotechnology can provide the technical power and tools that will enable those developing new diagnostics, therapeutics, and preventives to keep pace with today’s explosion in knowledge.
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