Monday, September 15, 2014

New publication uses PolySciTech PLGA-cysteine (PolyVivo AI25) as part of cancer treatment by targeted delivery of apoptosis inducing cytochrome C

PolySciTech (www.polyscitech.com) provides a wide array of reactive intermediate polymers. One of our products AI25 (PLGA-Cysteine ethyl ester endcap) was recently utilized in a publication in which it was conjugated to cytochrome C in order control the time and nature of drug release. Read more: Read More: Morales-Cruz, Moraima, Cindy M. Figueroa, Tania González-Robles, Yamixa Delgado, Anna Molina, Jessica Méndez, Myraida Morales, and Kai Griebenow. "Activation of caspase-dependent apoptosis by intracellular delivery of cytochrome c-based nanoparticles." Journal of nanobiotechnology 12, no. 1 (2014): 33. Full-Text: http://www.biomedcentral.com/content/pdf/s12951-014-0033-9.pdf

“Abstract: Background: Cytochrome c is an essential mediator of apoptosis when it is released from the mitochondria to the cytoplasm. This process normally takes place in response to DNA damage, but in many cancer cells (i.e., cancer stem cells)it is disabled due to various mechanisms. However, it has been demonstrated that the targeted delivery of Cytochrome c directly to the cytoplasm of cancer cells selective initiates apoptosis in many cancer cells. In this work we designed a novel nano-sized smart Cytochrome c drug delivery system to induce apoptosis in cancer cells upon delivery. Results: Cytochrome c was precipitated with a solvent-displacement method to obtain protein nanoparticles. The size of the Cytochrome c nanoparticles obtained was 100-300 nm in diameter depending on the conditions used, indicating good potential to passively target tumors by the Enhanced Permeability and Retention effect. The surface of Cytochrome c nanoparticles was decorated with poly (lactic-co-glycolic) acid-SH via the linker succinimidyl 3-(2-pyridyldithio)propionate to prevent premature dissolution during delivery. The linker connecting the polymer to the protein nanoparticle contained a disulfide bond thus allowing polymer shedding and subsequent Cytochrome c release under intracellular reducing conditions. A cell-free caspase-3 assay revealed more than 80% of relative caspase activation by Cytochrome c after nanoprecipitation and polymer modification when compared to native Cytochrome c. Incubation of HeLa cells with the Cytochrome c based-nanoparticles showed significant reduction in cell viability after 6 hours while native Cytochrome c showed none. Confocal microscopy confirmed the induction of apoptosis in HeLa cells when they were stained with 4’,6-diamidino-2-phenylindole and propidium iodide after incubation with the Cytochrome c-based nanoparticles. Conclusions: Our results demonstrate that the coating with a hydrophobic polymer stabilizes Cytochrome c nanoparticles allowing for their delivery to the cytoplasm of target cells. After smart release of Cytochrome c intothe cytoplasm, it induced programmed cell death. Keywords: Drug delivery, Protein nanoparticles, PLGA, Passive targeting, Triggered release”
Post a Comment