Wednesday, June 15, 2016

PEG precursor from PolySciTech used as part of folate-mediated delivery system development for brain cancer treatment

PolySciTech Division of Akina, Inc. (www.polyscitech.com) provides a wide array of polymers including heterobifunctional PEG precursors. Recently PolyVivo AE003 (Folate-PEG-COOH (3000Da)) was used by researchers at University of Puerto Rico to develop a folate-mediated delivery system for targeted application of cytochrome c, a protein that initiates apoptosis (cell-death). This research holds promise for enhanced chemotherapy techniques to kill off tumor cells while minimalizing toxic side-effects against normal cells. Read more: Morales-Cruz, Moraima, Alejandra Cruz-MontaƱez, Cindy M. Figueroa, Tania Gonzalez-Robles, Josue Davila, Mikhail Inyushin, Sergio A. Loza-Rosas et al. "Combining stimulus-triggered release and active targeting strategies improves cytotoxicity of cytochrome c nanoparticles in tumor cells." Molecular Pharmaceutics (2016). http://pubs.acs.org/doi/abs/10.1021/acs.molpharmaceut.6b00461


“Proteins often possess highly specific biological activities that make them potential therapeutics, but their physical and chemical instabilities during formulation, storage, and delivery have limited their medical use. Therefore, engineering of nano-sized vehicles to stabilize protein therapeutics and to allow for targeted treatment of complex diseases, such as cancer, is of considerable interest. A micelle-like nanoparticle (NP) was designed for both, tumor targeting and stimulus-triggered release of the apoptotic protein cytochrome c (Cyt c). This system is composed of a Cyt c NP stabilized by a folate-receptor targeting amphiphilic copolymer (FA-PEG-PLGA) attached to Cyt c through a redox-sensitive bond. FA-PEG-PLGA-S-S-Cyt c NPs exhibited excellent stability under extracellular physiological conditions, whereas once in the intracellular reducing environment, Cyt c was released from the conjugate. Under the same conditions, the folate-decorated NP reduced folate receptor positive HeLa cell viability to 20% while the same complex without FA only reduced it to 80%.  Confocal microscopy showed that the FA-PEG-PLGA-S-S-Cyt c NPs were internalized by HeLa cells and were capable of endosomal escape.  The specificity of the folate receptor-mediated internalization was confirmed by the lack of uptake by two folate receptor deficient cell lines: A549 and NIH-3T3. Finally, the potential as anti-tumor therapy of our folate-decorated Cyt c-based NPs was confirmed with an in vivo brain tumor model. In conclusion, we were able to create a stable, selective, and smart nanosized Cyt c delivery system.”
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