John Garner

Fluorescent-PLGA and PLGA-PEG-Mal from PolySciTech used in development of gastric/colorectal-cancer targeting nanoparticles.

Blog Post created by John Garner on Oct 1, 2018

Kennedy, 2018 nanoparticles cancer polyscitech CD44v6.jpg

Cancer cells present a variety of surface proteins and markers which can be used to both differentiate them from normal, healthy cells as well as useful as targets for treating the cancer cell. In this way, the antibody counter-part to the surface marker can be conjugated to a nanoparticle making it selectively ‘sticky’ to the cancer cell. This is a powerful technique to improve the efficacy of drugs against cancer cells with less toxicity against healthy cells.  Recently, researchers at Universidade do Porto, Universitário de Ciências da Saúde (Portugal), and Queen’s University Belfast (UK) used PLGA-FKR648 (PolyVivo AV015) and PLGA-PEG-Mal (PolyVivo AI110) from PolySciTech (www.polyscitech.com) to generate fluorescent, targeted nanoparticles for treatment of gastric and colorectal cancer. This research holds promise for improved therapies against this difficult to treat and often fatal disease. Read more: Kennedy, Patrick J., Flavia Sousa, Daniel Ferreira, Carla Pereira, Marika Nestor, Carla Oliveira, Pedro L. Granja, and Bruno Sarmento. "Fab-conjugated PLGA nanoparticles effectively target cancer cells expressing human CD44v6." Acta Biomaterialia (2018). https://www.sciencedirect.com/science/article/pii/S1742706118305725

 

“Abstract: Targeting of CD44 isoforms containing exon v6 (CD44v6) represents a viable strategy for the therapy and/or early diagnosis of metastatic cancers of the epithelium (e.g. gastric and colorectal cancer). We developed and characterized for the first time poly(lactic-co-glycolic acid) (PLGA)-based nanoparticles (NPs) modified with polyethylene glycol (PEG) and engrafted, by site-directed conjugation, with an engineered human Fab that specifically target human CD44v6 (v6 Fab-PLGA NPs). The v6 Fab-PLGA NPs display spherical morphology around 300 nm and are negatively charged. They strongly bound to a CD44v6-derived peptide and, more importantly, to cells that endogenously and exogenously express CD44v6, but not to non-expressing cells and cells expressing the standard isoform of CD44. The v6 Fab-PLGA NPs also recognized CD44v6 in tumor sections from cells grown subcutaneously within mice. The NPs had nominal cytotoxicity at 50 µg/mL and withstood simulated intestinal fluid exposure. Interestingly, v6 Fab-PLGA NPs cryopreserved in 10% trehalose and long-term stored maintained specific cell binding. In conclusion, we envision NPs targeting CD44v6 as potential in vivo diagnostic agents and/or as anti-cancer agents in patients previously stratified with CD44v6+ carcinomas. Statement of Significance: The v6 Fab-PLGA NPs displayed many favorable qualities as a potential CD44v6-targeted drug and/or diagnostic delivery agent. The NPs were designed for optimal ligand orientation and for immediate administration into humans. NPs strongly bind to cells that endogenously and exogenously express CD44v6, but not to non-expressing cells and cells expressing the standard isoform of CD44. Binding ability was retained after freeze-drying and long-term storage, providing evidences, for the first time, on the stability of Fab-functionalized NPs. These NPs can potentially be used as an in vivo diagnostic from parenteral or oral/rectal administration. Keywords: Human CD44v6 Targeted drug delivery Antibody-conjugated nanoparticles PLGA nanoparticles Theranostics”

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