Donato Colangelo | Università degli Studi del Piemonte Orientale (original) (raw)

Papers by Donato Colangelo

Nanomaterials, Nov 6, 2019

Tumor-targeted drug-loaded nanocarriers represent innovative and attractive tools for cancer ther... more Tumor-targeted drug-loaded nanocarriers represent innovative and attractive tools for cancer therapy. Several magnetic nanoparticles (MNPs) were analyzed as potential tumor-targeted drug-loaded nanocarriers after functionalization with anti-Met oncogene (anti-Met/HGFR) monoclonal antibody (mAb) and doxorubicin (DOXO). Their cytocompatibility, stability, immunocompetence (immunoprecipitation), and their interactions with cancer cells in vitro (Perl's staining, confocal microscopy, cytotoxic assays: MTT, real time toxicity) and with tumors in vivo (Perl's staining) were evaluated. The simplest silica-and calcium-free mAb-loaded MNPs were the most cytocompatible, the most stable, and showed the best immunocompetence and specificity. These mAb-functionalized MNPs specifically interacted with the surface of Met/HGFR-positive cells, and not with Met/HGFR-negative cells; they were not internalized, but they discharged in the targeted cells DOXO, which reached the nucleus, exerting cytotoxicity. The presence of mAbs on DOXO-MNPs significantly increased their cytotoxicity on Met/HGFR-positive cells, while no such effect was detectable on Met/HGFR-negative cells. Bare MNPs were biocompatible in vivo; mAb presence on MNPs induced a better dispersion within the tumor mass when injected in situ in Met/HGFR-positive xenotumors in NOD/SCID-γ null mice. These MNPs may represent a new and promising carrier for in vivo targeted drug delivery, in which applied gradient and alternating magnetic fields can enhance targeting and induce hyperthermia respectively.

Pharmaceutics, Jun 12, 2023

This article is an open access article distributed under the terms and conditions of the Creative... more This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY

Neuropeptides, Apr 1, 2001

Three types of tachykinin receptors, namely NK1, NK2 and NK3, are known to preferentially interac... more Three types of tachykinin receptors, namely NK1, NK2 and NK3, are known to preferentially interact with substance P (SP), neurokinin A (NKA) and neurokinin B (NKB), respectively. We previously demonstrated that NK1 and NK2 receptors are present on human monocytes, SP and NKA inducing superoxide anion production and tumor necrosis factor-alpha (TNF-alpha) mRNA expression. NK2 receptor stimulation also triggered an enhanced respiratory burst in monocytes isolated from rheumatoid arthritis (RA) patients. This study was aimed to evaluate the in vitro and ex-vivo effects of cyclosporin A (CsA) on tachykinins-evoked TNF-alpha release from monocytes of healthy donors and RA patients. CsA (100 ng/ml) potently inhibited phorbol ester- and tachykinin-evoked TNF-alpha secretion. In RA patients treated with CsA (Sandimmun Neoral 2.5 mg/kg/day, a significant time-dependent reduction in TNF-alpha secretion from monocytes was measured. This may contribute to the CsA therapeutic activity in RA.

Molecular Therapy, May 1, 2015

and injected with lipase inhibitor, further verifying that this genetic approach markedly diminis... more and injected with lipase inhibitor, further verifying that this genetic approach markedly diminished hepatic lipid synthesis. In BAT, Fgf21 transfer induced a "super-brown" phenotypic change, which was accompanied by elevated expression of a panel of vital genes for adaptive thermogenesis, such as Ucp1, Pgc1-alpha, Cidea, Dio2 and Elovl3. Collectively, our findings unveil that the triglyceride-lowering effect of cold exposure can be fully recapitulated by liver-specific delivery of the Fgf21 using a hydrodynamics-based procedure, indicating that this new approach may provide an alternative and more acceptable option for hyperlipidemia therapy in humans.

Pharmaceutics

New therapeutic strategies are required in cancer therapy. Considering the prominent role of tumo... more New therapeutic strategies are required in cancer therapy. Considering the prominent role of tumor-associated macrophages (TAMs) in the development and progression of cancer, the re-education of TAMs in the tumor microenvironment (TME) could represent a potential approach for cancer immunotherapy. TAMs display an irregular unfolded protein response (UPR) in their endoplasmic reticulum (ER) to endure environmental stress and ensure anti-cancer immunity. Therefore, nanotechnology could be an attractive tool to modulate the UPR in TAMs, providing an alternative strategy for TAM-targeted repolarization therapy. Herein, we developed and tested polydopamine-coupled magnetite nanoparticles (PDA-MNPs) functionalized with small interfering RNAs (siRNA) to downregulate the protein kinase R (PKR)-like ER kinase (PERK) expression in TAM-like macrophages derived from murine peritoneal exudate (PEMs). After the evaluation of the cytocompatibility, the cellular uptake, and the gene silencing effic...

International Journal of Molecular Sciences

Clinical knowledge about SARS-CoV-2 infection mechanisms and COVID-19 pathophysiology have enormo... more Clinical knowledge about SARS-CoV-2 infection mechanisms and COVID-19 pathophysiology have enormously increased during the pandemic. Nevertheless, because of the great heterogeneity of disease manifestations, a precise patient stratification at admission is still difficult, thus rendering a rational allocation of limited medical resources as well as a tailored therapeutic approach challenging. To date, many hematologic biomarkers have been validated to support the early triage of SARS-CoV-2-positive patients and to monitor their disease progression. Among them, some indices have proven to be not only predictive parameters, but also direct or indirect pharmacological targets, thus allowing for a more tailored approach to single-patient symptoms, especially in those with severe progressive disease. While many blood test-derived parameters quickly entered routine clinical practice, other circulating biomarkers have been proposed by several researchers who have investigated their reliab...

Nutrients

As lactoferrin is a nutritional supplement with proven antiviral and immunomodulatory abilities, ... more As lactoferrin is a nutritional supplement with proven antiviral and immunomodulatory abilities, it may be used to improve the clinical course of COVID-19. The clinical efficacy and safety of bovine lactoferrin were evaluated in the LAC randomized double-blind placebo-controlled trial. A total of 218 hospitalized adult patients with moderate-to-severe COVID-19 were randomized to receive 800 mg/die oral bovine lactoferrin (n = 113) or placebo (n = 105), both given in combination with standard COVID-19 therapy. No differences in lactoferrin vs. placebo were observed in the primary outcomes: the proportion of death or intensive care unit admission (risk ratio of 1.06 (95% CI 0.63–1.79)) or proportion of discharge or National Early Warning Score 2 (NEWS2) ≤ 2 within 14 days from enrollment (RR of 0.85 (95% CI 0.70–1.04)). Lactoferrin showed an excellent safety and tolerability profile. Even though bovine lactoferrin is safe and tolerable, our results do not support its use in hospitaliz...

Viruses

More than three years have passed since the first case, and COVID-19 is still a health concern, w... more More than three years have passed since the first case, and COVID-19 is still a health concern, with several open issues such as the lack of reliable predictors of a patient’s outcome. Osteopontin (OPN) is involved in inflammatory response to infection and in thrombosis driven by chronic inflammation, thus being a potential biomarker for COVID-19. The aim of the study was to evaluate OPN for predicting negative (death or need of ICU admission) or positive (discharge and/or clinical resolution within the first 14 days of hospitalization) outcome. We enrolled 133 hospitalized, moderate-to-severe COVID-19 patients in a prospective observational study between January and May 2021. Circulating OPN levels were measured by ELISA at admission and at day 7. The results showed a significant correlation between higher plasma concentrations of OPN at hospital admission and a worsening clinical condition. At multivariate analysis, after correction for demographic (age and gender) and variables o...

Nutrients

Langmuir, 2018

New biomimetic magnetite nanoparticles (hereafter BMNPs) with sizes larger than most common super... more New biomimetic magnetite nanoparticles (hereafter BMNPs) with sizes larger than most common superparamagnetic nanoparticles were produced in the presence of the recombinant MamC protein from Magnetococcus marinus MC-1 and functionalized with doxorubicin (DOXO) intended as potential drug nanocarriers. Unlike inorganic magnetite nanoparticles, in BMNPs the MamC protein controls their size and morphology, providing them with magnetic properties consistent with a large magnetic moment per particle; moreover, it provides the nanoparticles with novel surface properties. BMNPs display the isoelectric point at pH 4.4, being strongly negatively charged at physiological pH (pH 7.4). This allows both (i) their functionalization with DOXO, which is positively charged at pH 7.4, and (ii) the stability of the DOXO−surface bond and DOXO release to be pH dependent and governed by electrostatic interactions. DOXO adsorption follows a Langmuir−Freundlich model, and the coupling of DOXO to BMNPs (binary biomimetic nanoparticles) is very stable at physiological pH (maximum release of 5% of the drug adsorbed). Conversely, when pH decreases, these electrostatic interactions weaken, and at pH 5, DOXO is released up to ∼35% of the amount initially adsorbed. The DOXO−BMNPs display cytotoxicity on the GTL-16 human gastric carcinoma cell line in a dose-dependent manner, reaching about ∼70% of mortality at the maximum amount tested, while the nonloaded BMNPs are fully cytocompatible. The present data suggest that BMNPs could be useful as potential drug nanocarriers with a drug adsorptionrelease governed by changes in local pH values.

PLOS ONE, Jun 19, 2018

Background Improving the knowledge of angiomyolipoma physiopathology might help in refining its p... more Background Improving the knowledge of angiomyolipoma physiopathology might help in refining its pharmacological treatment. We investigated if angiomyolipoma cells have migratory properties, how their growth and motility can be influenced by the hormonal milieu, and if this can be related to a specific gender. Methods Primary cells were isolated from angiomyolipomas surgically resected for therapeutical reasons in a female and in a male patient. The genetic control demonstrated no TSC2 deletion. Bi-(wound healing) and three-dimensional (transwell assay) migration were analyzed in vitro in basal conditions and under the influence of 17β-estradiol and SDF-1α. Results Treatment up to 72 hours with 17-β-estradiol (0.1-100 nM), tamoxifen (0.2-20 μM) or with both, does not modify angiomyolipoma cells proliferation. On the other hand, SDF-1α and 17-β-estradiol treatment induce a significant motility increase (both bi-and three-dimensional) which becomes evident already after 2 hours of incubation. Angiomyolipoma cells express mRNA coding for SDF-1α and 17-β-estradiol receptors and secrete both the metalloproteases principally involved in malignant phenotype acquisition, i.e. MMP-2 and MMP-9. Conclusion Angiomyolipoma cells behave similarly, despite their different source. Primary angiomyolipoma cells migrate in response to hormonal milieu and soluble factors, and produce active metalloproteases, both aspects being consistent with the theory claiming they can migrate to the lungs (and/or other organs) and colonizing them. No main feature, among the aspects we analyzed, seems to be referable to the gender of origin.

Nanomaterials, 2022

Luminescent nanoparticles are innovative tools for medicine, allowing the imaging of cells and ti... more Luminescent nanoparticles are innovative tools for medicine, allowing the imaging of cells and tissues, and, at the same time, carrying and releasing different types of molecules. We explored and compared the loading/release ability of diclofenac (COX-2 antagonist), in both undoped- and luminescent Terbium3+ (Tb3+)-doped citrate-coated carbonated apatite nanoparticles at different temperatures (25, 37, 40 °C) and pHs (7.4, 5.2). The cytocompatibility was evaluated on two osteosarcoma cell lines and primary human osteoblasts. Biological effects of diclofenac-loaded-nanoparticles were monitored in an in vitro osteoblast’s cytokine–induced inflammation model by evaluating COX-2 mRNA expression and production of PGE2. Adsorption isotherms fitted the multilayer Langmuir-Freundlich model. The maximum adsorbed amounts at 37 °C were higher than at 25 °C, and particularly when using the Tb3+ -doped particles. Diclofenac-release efficiencies were higher at pH 5.2, a condition simulating a loc...

Anticancer research, 1992

We have in this study used the 3-(4,5-dimethyl-2- thiazoyl) -2,5-diphenyl 2-H-tetrazolium bromide... more We have in this study used the 3-(4,5-dimethyl-2- thiazoyl) -2,5-diphenyl 2-H-tetrazolium bromide (MTT) end point in our histoculture drug-response assay. We have previously demonstrated that the formazan crystals formed by MTT reduction by mitochondrial succinate dehydrogenase reflect polarized light and can be measured by pixel analysis in intact tissue. The results described here indicate a total specificity of 93.8% and a total accuracy of 74.6% of the MTT end point for drug response in histoculture correlating with nine different human xenograft tumors grown in nude mice with respect to the in vivo drug response data. This in vitro system allows prediction of positive and negative responses to drugs, with a rate of 70% and 71.8%, respectively. The system described here has potential for clinical use because of the possibility of simultaneous description of the MTT values and heterogeneous response to drugs within individual tumors.

Neuropeptides, 1994

Despite extensive knowledge of the pulmonary diffuse neuroendocrine system, the chemical coding o... more Despite extensive knowledge of the pulmonary diffuse neuroendocrine system, the chemical coding of the single and grouped endocrine cells is far from complete. In this study, the occurrence of 7B2, a highly conserved pituitary protein present in many neural and endocrine tissues, is

Journal of Pharmacy and Pharmacology, 1994

A water-oil microemulsion and an aqueous solution, both carrying pertechnetate, were injected sub... more A water-oil microemulsion and an aqueous solution, both carrying pertechnetate, were injected subcutaneously in rabbits; release was observed by imaging the administration sites with a gamma-camera. Disappearance from the injection site of pertechnetate in aqueous solution was about ten times faster than that of pertechnetate in a microemulsion.

Viruses

SARS-CoV-2 is the etiological agent of COVID-19, an extremely heterogenous disease that can cause... more SARS-CoV-2 is the etiological agent of COVID-19, an extremely heterogenous disease that can cause severe respiratory failure and critical illness. To date, reliable biomarkers allowing for early patient stratification according to disease severity are still lacking. Calcitonin gene-related peptide (CGRP) is a vasoactive neuropeptide involved in lung pathophysiology and immune modulation and is poorly investigated in the COVID-19 context. In this observational, prospective cohort study, we investigated the correlation between CGRP and clinical disease evolution in hospitalized moderate to severe COVID-19 patients. Between January and May 2021 (Italian third pandemic wave), 135 consecutive SARS-CoV-2 patients were diagnosed as being eligible for the study. Plasma CGRP level evaluation and routine laboratory tests were performed on blood samples collected at baseline and after 7 days of hospitalization. At baseline, the majority our patients had a moderate to severe clinical presentati...

Particle & Particle Systems Characterization, 2019

surface/volume ratio, may represent one of the possible alternatives, since they are efficient mu... more surface/volume ratio, may represent one of the possible alternatives, since they are efficient multifunctional devices for a targeted chemotherapy. [1,2] Moreover, they can also be used in theranostics, as they can simultaneously be used (either by themselves or functionalized) for diagnostics. [1,3-5] Magnetic nanoparticles (MNPs), especially magnetite (Fe 3 O 4), are one of the most demanded NPs because of their magnetic properties, which allow, on one hand, their guidance toward the target by external magnetic fields (continuous gradient magnetic field) [5-7] and, on the other, to mediate hyperthermia (locally increasing the temperature by the application of an alternating magnetic field), thus inducing the apoptosis of tumor cells, which are more sensitive than normal healthy cells. [8-10] MNPs are generally produced by two different strategies: i) coprecipitation of iron salts in basic aqueous media possibly stabilized by biocompatible surfactants/polymer; ii) thermal decomposition of organometallic precursors in highboiling nonpolar organic solvents at elevated temperatures (≈200-360 °C), which allows a great control of the size of the MNPs, their monodispersity, and uniformity. [11] However, these methods have some drawbacks, associated to the use of high Novel MamC-mediated biomimetic magnetic nanoparticles (BMNPs) are proposed as valuable carriers for targeted chemotherapy because of the size (36 ± 12 nm) and of surface properties conferred by MamC coating. They are super-paramagnetic at room and body temperatures, have a large magnetic moment per particle, mediate hyperthermia, are cytocompatible, and, having a negative surface charge at physiological pH, can be efficiently coupled with DOXOrubicin (DOXO) and a monoclonal antibody (mAb) directed against the human Met/hepatocyte growth factor receptor (overexpressed in many cancers) displaying coupling stability, while releasing DOXO at acidic pH. This release can be enhanced by hyperthermia. The DOXO-mAb-BMNPs selectively recognize Met, bind efficiently to Met + tumor cells, and discharge DOXO within their nuclei more efficiently than DOXO-BMNPs, exerting cytotoxicity. These data represent proof of concept for future in vivo experiments in which the controlled dual targeting (mAb-mediated and magnetic) approach and combined (chemotherapy and hyperthermia) therapy will be studied.

Langmuir : the ACS journal of surfaces and colloids, Jan 30, 2015

Multifunctional biomimetic nanoparticles (NPs) are acquiring increasing interest as carriers in m... more Multifunctional biomimetic nanoparticles (NPs) are acquiring increasing interest as carriers in medicine and basic research since they can efficiently combine labels for subsequent tracking, moieties for specific cell targeting, and bioactive molecules, e.g., drugs. In particular, because of their easy synthesis, low cost, good biocompatibility, high resorbability, easy surface functionalization, and pH-dependent solubility, nanocrystalline apatites are promising candidates as nanocarriers. This work describes the synthesis and characterization of bioinspired apatite nanoparticles to be used as fluorescent nanocarriers targeted against the Met/hepatocyte growth factor receptor, which is considered a tumor associated cell surface marker of many cancers. To this aim the nanoparticles have been labeled with Fluorescein-5-isothiocyanate (FITC) by simple isothermal adsorption, in the absence of organic, possibly toxic, molecules, and then functionalized with a monoclonal antibody (mAb) d...

British Journal of Pharmacology, 2001

Macrophage Stimulating Protein (MSP), a serum factor related to Hepatocyte Growth Factor, was ori... more Macrophage Stimulating Protein (MSP), a serum factor related to Hepatocyte Growth Factor, was originally discovered to stimulate chemotaxis of murine resident peritoneal macrophages. MSP is the ligand for Ron, a member of the Met subfamily of tyrosine kinase receptors. The eects of MSP on human macrophages and the role played in human pathophysiology have long been elusive. 2 We show here that human recombinant MSP (hrMSP) evokes a dose-dependent superoxide anion production in human alveolar and peritoneal macrophages as well as in monocyte-derived macrophages, but not in circulating human monocytes. Consistently, the mature Ron protein is expressed by the MSP responsive cells but not by the unresponsive monocytes. The respiratory burst evoked by hrMSP is quantitatively higher than the one induced by N-formylmethionyl-leucylphenylalanine and similar to phorbol myristate acetate-evoked one. 3 To investigate the mechanisms involved in NADPH oxidase activation, leading to superoxide anion production, dierent signal transduction inhibitors were used. By using the non selective tyrosine kinase inhibitor genistein, the selective c-Src inhibitor PP1, the tyrosine phosphatase inhibitor sodium orthovanadate, the phosphatidylinositol 3-kinase inhibitor wortmannin, the p38 inhibitor SB203580, the MEK inhibitor PD098059, we demonstrate that hrMSP-evoked superoxide production is mediated by tyrosine kinase activity, requires the activation of Src but not of PI 3kinase. We also show that MAP kinase and p38 signalling pathways are involved. 4 These results clearly indicate that hrMSP induces the respiratory burst in human macrophages but not in monocytes, suggesting for the MSP/Ron complex a role of activator as well as of possible marker for human mature macrophages.

The fourteenth and fifteenth authors, Antonia Follenzi and Maria Prat, should be noted as con-tri... more The fourteenth and fifteenth authors, Antonia Follenzi and Maria Prat, should be noted as con-tributing equally to this work. In the Author Contributions section, Antonia Follenzi (AF) should be listed as one of the persons who conceived and designed the experiments, contributed reagents/materials/analysis tools, and wrote the paper in addition to analyzed the data.

Nanomaterials, Nov 6, 2019

Pharmaceutics, Jun 12, 2023

Neuropeptides, Apr 1, 2001

Molecular Therapy, May 1, 2015

Pharmaceutics

International Journal of Molecular Sciences

Nutrients

Viruses

Nutrients

Langmuir, 2018

PLOS ONE, Jun 19, 2018

Nanomaterials, 2022

Anticancer research, 1992

Neuropeptides, 1994

Journal of Pharmacy and Pharmacology, 1994

Viruses

Particle & Particle Systems Characterization, 2019

Langmuir : the ACS journal of surfaces and colloids, Jan 30, 2015

British Journal of Pharmacology, 2001