Friday, June 26, 2020

Mal-PEG-PLGA from PolySciTech used in development of bevacizumab-nanoparticle based therapy for treatment of colorectal cancer


Colorectal cancer is one of the most common cancers in the world and is very difficult to treat effectively. Recently, Researchers at i3S, INEB, and Universidade do Porto (Portugal) used PLGA-PEG-Mal (AI110) from PolySciTech (www.polyscitech.com) as part of development of targeted nanoparticles loaded with bevacizumab to treat colon cancer. This research holds promise to improve therapies against this disease. Read more: Baião, Ana, Flávia Sousa, Ana Vanessa Oliveira, Carla Oliveira, and Bruno Sarmento. "Effective intracellular delivery of bevacizumab via PEGylated polymeric nanoparticles targeting the CD44v6 receptor in colon cancer cells." Biomaterials Science (2020). https://pubs.rsc.org/en/content/articlelanding/2020/bm/d0bm00556h/unauth#!divAbstract

“Abstract: Colorectal cancer (CRC) is one of the most common and deadly cancers in the world, mainly due to its metastatic and metabolic ability. The CD44 receptor isoform containing exon 6 (CD44v6) is a transmembrane protein that plays an important role in the establishment of tumors and metastasis, which make this molecule a potential target for therapy and diagnosis of tumors. Aiming at a targeted therapy, the anti-VEGF monoclonal antibody (mAb) bevacizumab was loaded into poly(lactic-co-glycolic acid)-polyethylene glycol (PLGA-PEG) nanoparticles (NPs) functionalized with an antibody fragment (Fab) specific for CD44v6-expressing human cancer cells. The sizes of NPs were in the range of 150–250 nm and they had a negative charge between −5 and −10 mV, with an association efficiency (AE) of bevacizumab of 86%. v6 Fab-PLGA-PEG NPs containing bevacizumab specifically bonded to the CD44v6 cell surface receptor and exhibited higher internalization into CD44v6+ epithelial cells than bare and (−) Fab-PLGA-PEG NPs. To understand the biological effect of NP targeting, the intracellular levels of bevacizumab and VEGF were evaluated after the incubation of targeted and untargeted NPs. The intracellular levels of bevacizumab were significantly higher in cells incubated with v6 Fab-PLGA-PEG NPs and these NPs resulted in a significant decrease in the intracellular VEGF compared to untargeted NPs and free bevacizumab. PLGA-PEG NPs, surface-functionalized with a v6-specific Fab, have the potential to intracellularly deliver bevacizumab into CD44v6 expressing cancer cells.”

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