Glucosylated Polymeric Micelles Actively Target a Breast Cancer Model. N Lecot*, R Glisoni*, N Oddone, J Benech, M Fernández, JP Gambini, O Cabral, A Sosnik. Advanced Therapeutics. *Authors equally contributed to this work. https://doi.org/10.1002/adtp.202000010
Abstract
This work investigates the potential of glycosylation to actively target nanodrug delivery systems to adult solid tumors overexpressing glucose transporters. The highly hydrophobic fluorescent compound curcumin (CUR) is nanoencapsulated within polymeric micelles of pristine and glucosylated poly(ethylene oxide)‐poly(propylene oxide) block copolymers, and their interaction with breast cancer (BC) cells is investigated in vitro and in vivo. The aqueous solubility of CUR is increased more than 50 000‐fold and spherical nanoparticles display size in the 40 to 500 nm range, as determined by transmission electron microscopy and by dynamic light scattering, respectively. Uptake studies conducted in the BC cell line 4T1 in vitro demonstrate that glucosylation enhances nanoparticle internalization. Finally, the ability of unmodified and glucosylated polymeric micelles to accumulate in female BALB/c mice bearing 4T1‐induced tumors is compared by ex vivo bioimaging with auspicious results.
Extracellular vesicles containing the transferrin receptor as nanocarriers of apotransferrin. VS Mattera, P Pereyra Gerber, RJ Glisoni, M Ostrowski, SV Verstraeten , JM Pasquini, JD Correale. J Neurochem. 2020. https://doi.org/10.1111/jnc.15019
Abstract
Previous work by our group has shown the pro‐differentiating effects of apotransferrin (aTf) on oligodendroglial cells in vivo and in vitro. Further studies showed the remyelinating effect of aTf in animal demyelination models such as hypoxia/ischemia, where the intranasal administration of human aTf provided brain neuroprotection and reduced white matter damage, neuronal loss, and astrogliosis in different brain regions. These data led us to search for a less invasive and controlled technique to deliver aTf to the CNS. To such end, we isolated extracellular vesicles (EVs) from human and mouse plasma and different neuron and glia conditioned media and characterized them based on their quality, quantity, identity, and structural integrity by western blot, dynamic light scattering, and scanning electron microscopy. All sources yielded highly pure vesicles whose size and structures were in keeping with previous literary evidence. Given that, remarkably, EVs from all sources analyzed contained Tf receptor 1 (TfR1) in their composition, we employed two passive cargo‐loading strategies which rendered successful EV loading with aTf, specifically through binding to TfR1. These results unveil EVs as potential nanovehicles of aTf to be delivered into the CNS parenchyma, and pave the way for further studies into their possible clinical application in the treatment of demyelinating diseases.
