3 research outputs found
Theranostic design of angiopepâ2 conjugated hyaluronic acid nanoparticles (Theraâangâchanps) for dual targeting a
Glioblastoma multiforme (GBM) has a mean survival of only 15 months. Tumour heterogeneity and bloodâbrain barrier (BBB) mainly hinder the transport of active agents, leading to late diagnosis, ineffective therapy and inaccurate followâup. The use of hydrogel nanoparticles, particularly hyaluronic acid as naturally occurring polymer of the extracellular matrix (ECM), has great potential in improving the transport of drug molecules and, furthermore, in facilitatating the early diagnosis by the effect of hydrodenticity enabling the T1 boosting of Gadolinium chelates for MRI. Here, crosslinked hyaluronic acid nanoparticles encapsulating gadolinium-diethylenetriamine pentaacetic acid (GdâDTPA) and the chemotherapeutic agent irinotecan (Thera-cHANPs) are proposed as theranostic nanovectors, with improved MRI capacities. Irinotecan was selected since currently repurposed as an alternative compound to the poorly effective temozolomide (TMZ), generally approved as the gold standard in GBM clinical care. Also, active crossing and targeting are achieved by theranostic cHANPs decorated with angiopepâ2 (Theraâ ANGâcHANPs), a dualâtargeting peptide interacting with low density lipoprotein receptor related proteinâ1(LRPâ1) receptors overexpressed by both endothelial cells of the BBB and glioma cells. Results showed preserving the hydrodenticity effect in the advanced formulation and internalization by the active peptideâmediated uptake of TheraâcHANPs in U87 and GSâ102 cells. Moreover, TheraâANGâcHANPs proved to reduce ironotecan time response, showing a significant cytotoxic effect in 24 h instead of 48 h