Preparation and Characterization of Inulin Coated Gold Nanoparticles for Selective Delivery of Doxorubicin to Breast Cancer Cells

A novel folate-targeted gold-based nanosystem for achieving selectivity towards folate receptor (FR) positive cells is proposed, by virtue of the fact that the FR is a molecularly targeted entity overexpressed in a wide spectrum of solid tumors. A new inulin-folate derivative (INU-FA) has been synthesized to act as coating agent for 40 nm gold nanoparticles. The obtained polymer-coated gold nanoparticles (Au@INU-FA) were characterized in terms of hydrodynamic radius, shape, zeta potential, and aqueous stability and were loaded with doxorubicin (Au@INU-FA/Doxo). Its release capability was tested in different release media. The selectivity of Au@INU-FA/Doxo system towards FRs-positive cancer cells was proved by the differences in the quantitative uptake using human breast cancer MCF7 as FR-positive cells and 16HBE epithelial as noncancer cell line. Furthermore, the folate-mediated uptake mechanism was studied by FRs-blocking experiments. On the whole Au@INU-FA/Doxo was able to be preferentially internalized into MCF7 cells proving a folate-mediated endocytosis mechanism which allowed a higher and selective cytotoxic effect towards cancer cells. The cytotoxicity profile was evaluated on both cancer and noncancer cell lines, displaying that folate-mediated targeting implied advantageous therapeutic effects, such as amplified drug uptake and increased anticancer activity towards MCF7 cancer cells

Prevalence of hepatic steatosis in patients with type 2 diabetes and response to glucose-lowering treatments. A multicenter retrospective study in Italian specialist care

Type 2 diabetes (T2D) is a risk factor for metabolic dysfunction-associated fatty liver disease (MAFLD), which is becoming the commonest cause of chronic liver disease worldwide. We estimated MAFLD prevalence among patients with T2D using the hepatic steatosis index (HSI) and validated it against liver ultrasound. We also examined whether glucose-lowering medications (GLM) beneficially affected HSI

Similar effectiveness of dapagliflozin and GLP-1 receptor agonists concerning combined endpoints in routine clinical practice: A multicentre retrospective study

Aims According to cardiovascular outcome trials, some sodium-glucose contransporter-2 inhibitors (SGLT2i) and glucagon-like peptide-1 receptor agonists (GLP-1RA) are recommended for secondary cardiovascular prevention in type 2 diabetes (T2D). In this real-world study, we compared the simultaneous reductions in HbA1c, body weight and systolic blood pressure after initiation of dapagliflozin or GLP-1RA as second or a more advanced line of therapy. Materials and methods DARWIN-T2D was a retrospective multi-centre study conducted at diabetes specialist clinics in Italy that compared T2D patients who initiated dapagliflozin or GLP-1RA (exenatide once weekly or liraglutide). Data were collected at baseline and at the first follow-up visit after 3 to 12 months. The primary endpoint was the proportion of patients achieving a simultaneous reduction in HbA1c, body weight and systolic blood pressure. To reduce confounding, we used multivariable adjustment (MVA) or propensity score matching (PSM). Results Totals of 473 patients initiating dapagliflozin and 336 patients initiating GLP-1RA were included. The two groups differed in age, diabetes duration, HbA1c, weight and concomitant medications. The median follow-up was 6 months in both groups. Using MVA or PSM, the primary endpoint was observed in 30% to 32% of patients, with no difference between groups. Simultaneous reduction of HbA1c, BP and SBP by specific threshold, as well as achievement of final goals, did not differ between groups. GLP-1RA reduced HbA1c by 0.3% more than the reduction achieved with dapagliflozin. Conclusion In routine specialist care, initiation of dapagliflozin can be as effective as initiation of a GLP-1RA for attainment of combined risk factor goals

Understanding the role of graphene oxide in the capture and eradication of circulating tumor cells

The capture of circulating cancer cells on functional biomaterials is expected to control metastatic spread of a tumor, which is related to good probability containing the progression of disease burden. (1) The physicochemical characteristics of a biomaterial surface highly affect cell recruitment and adhesion, which is of great importance in such applications. Here, we designed a poly(caprolactone)-based nanocompsite scaffold, henceforth PCLMF-GO, to simultaneously recruit and kill circulating cancer cells by tuning physicochemical features of the scaffold surface through nitrogen plasma activation and hetero-phase graphene oxide (GO) covalent functionalization. Nitrogen plasma activation was used for scaffold engineering to provide functionalization of the scaffold surface with reactive amines, even if keeping bulk properties of the virgin polymeric material, and to enhance cell adhesion properties of hydrophobic polymers.(2) In this work, we demonstrate plasma-induced microfiber surface functionalization coupling DSC, FT-IR, SEM, AFM, XPS and MS-NMR analyses, corroborating the starting hypothesis that GO was covalently bonded at the scaffold surface. Surface immobilization of GO implies clever cell adhesion and proliferation, promoting the selective in vitro recruitment of breast cancer cells (MCF-7) instead of fibroblasts (HDFa). We also display that GO deposition, thanks to the high near-infrared (NIR) absorbance, enable the discrete photothermal eradication of the captured cancer cells in situ (≈ 98%). Moreover, this technology can be used in frontier medical practices to capture circulating cancer cells in patients and, after proper ex vivo propagation, to develop biomarkers and tailor-made anticancer therapies. 1. Griffith, OL et al. (2011) Breast Cancer Res. 13: 230 2. Lopez, L. C. et al. (2007) Plasma Process. Polym. 4:S402–S40

Photothermal ablation of cancer cells using folate-coated gold/graphene oxide composite

A new tumor targeted polymer-coated gold/graphene hybrid has been developed for achieving simultaneously thermoablation and chemoterapy of folate receptor-positive cancer cells

Inulin-Ethylenediamine Coated SPIONs Magnetoplexes: A Promising Tool for Improving siRNA Delivery

Purpose: An inulin based polycation (Inu-EDA) has been synthesized by the grafting of ethylenediamine molecules onto inulin backbone. The obtained inulin copolymer has been though to coat SPIONs (IC-SPIONs) and obtain stable magnetoplexes by complexation of IC-SPIONs with a model duplexed siRNA, for improving oligonucleotide transfection efficiency. Methods: The physical-chemical characteristics of IC-SPIONs and IC-SPIONs/siRNA magnetoplexes have been investigated by scanning and transmission electron microscopies, dynamic light scattering, FT-IR and qualitative surface elementary analysis. Cell compatibility and internalization in vitro of IC-SPIONs have been evaluated by MTS and fluorescence microscopy respectively on cancer (HCT116) and normal human (16HBE) cells. The efficiency of gene silencing effect of magnetoplexes was studied on both tumoral (JHH6) and non tumoral (16HBE) cell lines also by applying an external magnet. Results: IC-SPIONs showed dimension of 30 nm and resulted cytocompatible on the tested cell lines; in the presence of an external magnet, the magnetic force enhanced the IC-SPIONs uptake inside cells. Magnetically improved transfection was observed in 16HBE cells under magnetofective conditions, in accordance with the IC-SPIONs uptake enhancement in the presence of an external magnet. Conclusions: These findings support the potential application of this system as a magnetically targeted drug delivery system. [Figure not available: see fulltext.

Near-Infrared Light Responsive Folate Targeted Gold Nanorods for Combined Photothermal-Chemotherapy of Osteosarcoma

Folate-targeted gold nanorods (GNRs) are proposed as selective theranostic agents for osteosarcoma treatment. An amphiphilic polysaccharide based graft-copolymer (INU-LA-PEG-FA) and an amino derivative of the α,β-poly(N-2-hydroxyethyl)-d,l-aspartamide functionalized with folic acid (PHEA-EDA-FA), have been synthesized to act as coating agents for GNRs. The obtained polymer-coated GNRs were characterized in terms of size, shape, zeta potential, chemical composition, and aqueous stability. They protected the anticancer drug nutlin-3 and were able to deliver it efficiently in different physiological media. The ability of the proposed systems to selectively kill tumor cells was tested on U2OS cancer cells expressing high levels of FRs and compared with human bronchial epithelial cells (16HBE) and human dermal fibroblasts (HDFa). The property of the nanosystems of efficiently controlling drug release upon NIR laser irradiation and of acting as an excellent hyperthermia agent as well as Two Photon Luminescence imaging contrast agents was demonstrated. The proposed folate-targeted GNRs have also been tested in terms of chemoterapeutic and thermoablation efficacy on tridimensional (3-D) osteosarcoma models

Folate-targeted gold nanorods for effective combined photothermal-chemotherapy of osteosarcoma

Osteosarcoma (OS) is the most common primary malignant neoplasm of bone. The annual incidence of osteosarcoma is 8-11 per million in the age group of 15-19 years. Despite its rarity, it has been reported to be the second leading cause of cancer-related deaths in children and young adults. In particular with regard to OS therapy, a variety of nanostructures have been exploited in the areas of OS imaging. Among them, Gold nanorods (AuNRs) have unique optical and chemical-physical properties that make them appealing for biomedical applications such as photothermal therapy, drug delivery and imaging of solid tumors. The noble metal core is biologically inert, contributing to low toxicity and good biocompatibility. Their large surface area and their high affinity for thiol groups allows their easy surface functionalization, so that therapeutic agents, targeting ligands and biocompatible coatings can be introduced. AuNRs also display the phenomenon of Surface Plasmon Resonance (SPR), resulting in large absorption band in the visible and near-Infra Red (NIR), whose wavelength depends on the AuNRs dimensions and shape. When laser-irradiated, AuNRs convert the absorbed radiation into heat and can act as two photon luminescence contrast agent. However AuNRs cannot be administered in vivo without a proper coating, due to their low stability in aqueous media

Hybrid Gold/Silica/Quantum-Dots supramolecular-nanostructures encapsulated in polymeric micelles as potential theranostic tool for targeted cancer therapy

Efficient theranostic tools are today more and more frequently represented by the nano-sized systems. In this paper, polymeric micelles were produced and exploited to encapsulate both an antitumor drug (Doxorubicin) and gold core–shell quantum dots nanoparticles (Au-SiO2/QDs). α,β-poly(N-hydroxyethyl)-DL-aspartamide (PHEA) was functionalized with lipoic acid (LA), polyethylenglycol (PEG), and folic acid (FA) pendant moieties to obtain a synthetic derivative (PHEA-LA-PEG-FA) able to self assemble in aqueous medium giving rise to the formation of polymeric micelles exposing on their surface both targeting groups (FA) and hydrophilic chains (PEG). The drug carrying ability of PHEA-LA-PEG-FA micelles was here studied along with the cytotoxity of the obtained nanostructures toward breast cancer cells employing doxorubicin as a model anticancer drug. Finally, the properties of the gold-shell QDs incorporated into the micelles as cells imaging agent and photothermal anticancer treatment tool were explored