Fluorescent PLGA-FKR648 from PolySciTech used in development of anticancer nanotherapeutics

 

Among brain cancers, glioblastoma is the most common and deadly primary malignant tumor in adults. In order to evaluate the efficacy of cancer therapeutics, it is important to replicate the tumor microenvironment so that the behavior of the medicine or delivery system matches that which is to be expected in-vivo. Researchers at Universidade do Porto (Portugal) used PLGA-FKR648 (Cat# AV015) from PolySciTech Division of Akina, Inc. (www.polyscitech.comto formulate traceable nanoparticles which can be observed by fluorescence techniques. They tested these nanoparticles against a novel model-cancer system consisting of carefully constructed artificial tumor microtissues grown in-vitro. This research holds promise to improve therapies against brain cancer. Read more: Martins, Cláudia, Catarina Pacheco, Catarina Moreira-Barbosa, Ângela Marques-Magalhães, Sofia Dias, Marco Araújo, Maria J. Oliveira, and Bruno Sarmento. "Glioblastoma immuno-endothelial multicellular microtissue as a 3D in vitro evaluation tool of anti-cancer nano-therapeutics." Journal of Controlled Release 353 (2023): 77-95. https://www.sciencedirect.com/science/article/pii/S0168365922007684

“Highlights: Glioblastoma heterotypic multicellular tumor microtissues (MCTMs) are generated. MCTMs mimic tumor organization, extracellular matrix production and necrosis. MCTMs respond to a tumor-targeted docetaxel (DTX) nanotherapy. MCTMs macrophages polarize into a M1-/M2-phenotype according to the nanotherapy. MCTMs exhibit a particular biomolecular cytokine signature after treatment. Abstract: Despite being the most prevalent and lethal type of adult brain cancer, glioblastoma (GBM) remains intractable. Promising anti-GBM nanoparticle (NP) systems have been developed to improve the anti-cancer performance of difficult-to-deliver therapeutics, with particular emphasis on tumor targeting strategies. However, current disease modeling toolboxes lack close-to-native in vitro models that emulate GBM microenvironment and bioarchitecture, thus partially hindering translation due to poorly predicted clinical responses. Herein, human GBM heterotypic multicellular tumor microtissues (MCTMs) are generated through high-throughput 3D modeling of U-251 MG tumor cells, tissue differentiated macrophages isolated from peripheral monocytes, and brain microvascular primary endothelial cells. GBM MCTMs mimicked tumor spatial organization, extracellular matrix production and necrosis areas. The bioactivity of a model drug, docetaxel (DTX), and of tumor-targeted DTX-loaded polymeric NPs with a surface L-Histidine moiety (H-NPs), were assessed in the MCTMs. MCTMs cell uptake and anti-proliferative effect was 8- and 3-times higher for H-NPs, respectively, compared to the non-targeted NPs and to free DTX. H-NPs provided a decrease of MCTMs anti-inflammatory M2-macrophages, while increasing their pro-inflammatory M1 counterparts. Moreover, H-NPs showed a particular biomolecular signature through reduced secretion of an array of medium cytokines (IFN-γ, IL-1β, IL-1Ra, IL-6, IL-8, TGF-β). Overall, MCTMs provide an in vitro biomimetic model to recapitulate key cellular and structural features of GBM and improve in vivo drug response predictability, fostering future clinical translation of anti-GBM nano-therapeutic strategies.”