Wednesday, October 15, 2014

New publication utilizes Mal-PEG-PLGA from PolySciTech for generating Her2 targeted, RNAse delivering, nanoparticle for cancer therapy.

PolySciTech (www.polyscitech.com) provides a wide array of Maleimide-PEG-PLGA and other reactive intermediates. Recently published PhD thesis of Neda Samadi from Utrecht University utilized Polyvivo AI20 to generate nanoparticles labelled with 11A4 protein for Her2 targeting and used these nanoparticles to deliver RNAse to tumor cells. Alone RNAse is innefective at preventing cancer cell growth but when encapsulated in the delivery system an IC50 of only 5uM was observed. Read more with full-text available here: Samadi, Neda, Marta M. Kijanka, Sabrina Oliveira, Tina Vermonden, Cornelus F. van Nostrum, Maryam Amidi, Paul MP van Bergen en Henegouwen, and W. E. Hennink. "Nanobody-Targeted and RNase-Loaded Nanoparticles Based on a Hydrophilic Polyester Aimed for Cancer Therapy." Biodegradable Nanoparticles Based on Aliphatic Polyesters; Towards Targeted Intracellular Delivery of Protein Therapeutics: 117. http://dspace.library.uu.nl/bitstream/handle/1874/292552/samadi.pdf?sequence=2#page=117

“Abstract: The aim of this study was to develop a nanomedicine based on a hydrophilic polyester (poly lactic-co-glycolic-co-hydroxymethyl glycolic acid; PLGHMGA) for targeted delivery of RNase A as a modality for cancer treatment. RNase-loaded pegylated PLGHMGA nanoparticles (NPs) of ~280 nm were prepared by a double emulsion solvent evaporation method. Encapsulated RNase was almost completely released within 12 days and it was shown that the enzymatic activity of the released protein was fully preserved. Ten % Maleimide-PEG-PLGA was added to the formulation to graft the Her2 targeted nanobody (11A4) at the surface of the NPs to render them specific for breast cancer cells. Alexa Fluor 532 labeled 11A4-decorated NPs showed substantially higher binding to and uptake by Her2 over-expressing cancer cells (Skbr3) than particles without nanobody. Interestingly, no binding of the nanobody-conjugated particles was observed onto Her2 negative cells (MDA-MB-231). The RNase-loaded 11A4-NPs exhibited a dose-dependent cytotoxicity with an IC50 of 5 μM, whereas free RNase was ineffective up to 100 μM. These results demonstrate that nanobody conjugated PLGHMGA NPs are promising carriers for targeted delivery of RNase.”
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