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”
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