Active targeting of cancer cells by CD44 binding peptide-functionalized oil core-based nanocapsules.

Selectivity in tumor targeting is one of the major issues in cancer treatment. Therefore, surface functionalization of drug delivery systems with active moieties, able to selectively target tumors, has become a worldwide-recognized strategy. The CD44 receptor is largely used as a biomarker, being overexpressed in several tumors, and consequently as a target thanks to the identification of the CD44 binding peptide. Here we implemented the CD44 binding peptide logic onto an oil core-polymer multilayer shell, taking into account and optimizing all relevant features of drug delivery systems, such as small size (down to 100 nm), narrow size distribution, drug loading capability, antifouling and biodegradability. Besides promoting active targeting, the oil core-based system enables the delivery of natural and synthetic therapeutic compounds. Biological tests, using curcumin as a bioactive compound and fluorescent tag, demonstrated that CD44 binding peptide-functionalized nanocapsules selectively accumulate and internalize in cancer cells, compared to the control, thanks to ligand-receptor binding.

Treatment of de novo femoro-popliteal lesions with a new Drug Coated Balloon: early experience of a single Center in the first 50 patients.

Angioplasty with drug-coated balloon (DCB) is an emerging and reliable method for the treatment of femoro-popliteal lesions. We report our experience with the Stellarex™ DCB in the first 50 patients. METHODS: From July 2015 to November 2017, 50 patients (41 M, 9F), medium age (64 ± 7.4 year) were subject to 33 angioplasties (PTAs) for femoro-popliteal lesions with a paclitaxel-coated balloon (Stellarex™). Based upon clinical data sixteen patients had severe claudication (56% - Rutherford class 3); ten patients suffered from ischemic rest pain (34% - Rutherford class 4); and five presented minor tissue loss (10% - Rutherford class 5). 42% of patients showed femoro-popliteal lesion TASC-II B, and 58% presented lesions pertaining to TASC-II C. RESULTS: Immediate technical success was 100% without perioperative complications. Primary patency rate was 94% at twelve months. In three cases restenosis (6%) was detected within a year from procedure, and a further PTA DCB was performed with primary assisted patency rates of 100% at twelve months. Two patients underwent major lower limb amputation. Three patients died during follow-up and one patient was lost at follow-up. CONCLUSION: DCB angioplasty with Stellarex™ is a viable alternative to traditional endovascular procedures proving satisfactory primary patency rates at twelve months. Based on our experience, treatment with DCB is a first choice technique for non-complex de novo lesions of the femoro - popliteal tract.

Covalently immobilized RGD gradient on PEG hydrogel scaffold influences cell migration parameters.

Understanding the influence of a controlled spatial distribution of biological cues on cell activities can be useful to design "cell instructive" materials, able to control and guide the formation of engineered tissues in vivo and in vitro. To this purpose, biochemical and mechanical properties of the resulting biomaterial must be carefully designed and controlled. In this work, the effect of covalently immobilized RGD peptide gradients on poly(ethylene glycol) diacrylate hydrogels on cell behaviour was studied. We set up a mechanical device generating gradients based on a fluidic chamber. Cell response to RGD gradients with different slope (0.7, 1 and 2 mM cm(-1)) was qualitatively and quantitatively assessed by evaluating cell adhesion and, in particular, cell migration, compared to cells seeded on hydrogels with uniform distribution of RGD peptides. To evaluate the influence of RGD gradient and to exclude any concentration effect on cell response, all analyses were carried out in a specific region of the gradients which displayed the same average concentration of RGD (1.5 mM). Results suggest that cells recognize the RGD gradient and adhere onto it assuming a stretched shape. Moreover, cells tend to migrate in the direction of the gradient, as their speed is higher than that of cells migrating on hydrogels with a uniform distribution of RGD and increases by increasing RGD gradient steepness. This increment is due to an augmentation of bias speed component of the mean squared speed, that is, the drift of the cell population migrating on the anisotropic surface provided by the RGD gradient.

Glycosylations of inosine and uridine nucleoside bases and synthesis of the new 1-(beta-D-glucopyranosyl)-inosine-5',6"-diphosphate.

Gluco- and ribosylation of the bases of sugar protected inosine and uridine were investigated, obtaining only adducts with beta-configuration at the new glycosidic carbon; stereospecific insertion of a sugar moiety at the 1-N of inosine was achieved either using a Mitsunobu approach (for ribosylation) or by direct coupling of 1-alpha-bromoglucose 13 with 2',3',5'-tri-O-acetylinosine for glucosylation. 1-(beta-D-glucosyl)-inosine, chosen as starting substrate for glucosylated analogs of cyclic IDP-ribose, was phosphorylated at the primary hydroxyls and tested in intramolecular pyrophosphate bond formation.