Biodegradable nanoparticles exposing a short anti-FLT1 peptide as antiangiogenic platform to complement docetaxel anticancer activity(171 views visite) Conte C, Moret F, Esposito D, Dal Poggetto G, Avitabile C, Ungaro F, Romanelli A, Laurienzo P, Reddi E, Quaglia F
Mater Sci Eng C Mater Biol Appl (ISSN: 0928-4931linking), 2019 Sep; 102: 876-886.
Keywords Parole chiave: Angiogenesis Inhibitors Pharmacology
, Animals
, Antineoplastic Agents Pharmacology
, Biocompatible Materials Pharmacology
, Cell Death Drug Effects
, Cell Line, Tumor
, Cell Membrane Drug Effects Metabolism
, Chickens
, Chorioallantoic Membrane Drug Effects Metabolism
, Docetaxel Pharmacology
, Human Umbilical Vein Endothelial Cells Drug Effects Metabolism
, Nanoparticles Chemistry
, Neovascularization, Physiologic Drug Effects
, Peptides Chemistry
, Polyesters Chemical Synthesis Chemistry
, Polyethylene Glycols Chemical Synthesis Chemistry
, Vascular Endothelial Growth Factor Receptor-1 Metabolism
Affiliations Affiliazioni: *** IBB - CNR ***
Department of Pharmacy, University of Napoli Federico II, Italy.
Department of Biology, University of Padova, Italy.
Institute for Polymers, Composites and Biomaterials, CNR, Pozzuoli, Napoli, Italy.
Institute of Biostructure and Bioimaging, CNR, Napoli, Italy.
References Riferimenti: Not available. Non disponibili.
Biodegradable nanoparticles exposing a short anti-FLT1 peptide as antiangiogenic platform to complement docetaxel anticancer activity
Inhibition of tumor angiogenesis is considered as a valuable clinical strategy to treat some tumors, although benefits in term of progression-free and overall survival have been modest. Recent findings have pushed toward the use of antiangiogenic drugs in combination with chemotherapy regimens to potentiate therapeutic outcome. Herein, we propose a novel type of biodegradable antiangiogenic core-shell polymeric nanoparticles (NPs) for the delivery of poorly water-soluble chemotherapeutics. An amphiphilic diblock copolymer of poly(ethyleneglycol)-poly(ε-caprolactone) (PEG-PCL) was conjugated with an anti-FLT1 hexapeptide (aFLT1) at -OH PEG end, mixed in appropriate ratios with a monomethoxy-PEG-PCL and nanoprecipitated to form core-shell aFLT1-bearing NPs (DBL(aFLT1)). DBL(aFLT1) were <100 nm, exposed aFLT1 on the surface and showed a higher thickness of the external hydrophilic shell as compared to NPs that do not bear aFLT1 (DBL). Very interestingly, DBL(aFLT1) showed an antiangiogenic activity in the human umbilical endothelial cells (HUVEC) tube formation assay three-fold higher than an equivalent dose of free aFLT1. To provide a proof-of-concept of DBL(aFLT1) potential in the delivery of conventional chemotherapeutics, docetaxel (DTX) was selected as model drug. DBL(aFLT1) entrapped DTX with high efficiency and sustained its release along time in simulated biological conditions. At a non-cytotoxic dose, DTX-loaded DBL(aFLT1) almost completely abolished tube formation in HUVEC while inhibition of DTX loaded DBL was significantly lower. The cytotoxicity of DTX-loaded NPs in HUVEC and triple negative breast cancer cells (MDA-MB-231) was not significantly different from that of the free drug in a wide range of concentrations and up to 72 h. Studies carried out in MDA-MB-231 cells implanted in chicken embryo chorioallantoic membranes (CAMs) evidenced an antiangiogenic activity of DTX-loaded DBL(aFLT1) higher as compared with that of both DTX-loaded DBL and free DTX. While cancer cell migration from the tumor site was unaffected, the anticancer activity of DTX-loaded NPs was higher than that of free DTX and maximized for DTX-DBL(aFLT1). In perspective, these results suggest that the delivery approach proposed here can be applied to other lipophilic chemotherapeutics devoid of relevant antiangiogenic properties to improve the final therapeutic response.
Biodegradable nanoparticles exposing a short anti-FLT1 peptide as antiangiogenic platform to complement docetaxel anticancer activity
Kim YH, Shin SW, Pellicano R, Fagoonee S, Choi IJ, Kim YI, Park B, Choi JM, Kim SG, Choi J, Park JY, Oh S, Yang HJ, Lim JH, Im JP, Kim JS, Jung HC, Ponzetto A, Figura N, Malfertheiner P, Choi IJ, Kook MC, Kim YI, Cho SJ, Lee JY, Kim CG, Park B, Nam BH, Bae SE, Choi KD, Choe J, Kim SO, Na HK, Choi JY, Ahn JY, Jung KW, Lee J, Kim DH, Chang HS, Song HJ, Lee GH, Jung HY, Seta T, Takahashi Y, Noguchi Y, Shikata S, Sakai T, Sakai K, Yamashita Y, Nakayama T, Leja M, Park JY, Murillo R, Liepniece-karele I, Isajevs S, Kikuste I, Rudzite D, Krike P, Parshutin S, Polaka I, Kirsners A, Santare D, Folkmanis V, Daugule I, Plummer M, Herrero R, Tsukamoto T, Nakagawa M, Kiriyama Y, Toyoda T, Cao X, Corral JE, Mera R, Dye CW, Morgan DR, Lee YC, Lin JT, Garcia Martin R, Matia Cubillo A, Lee SH, Park JM, Han YM, Ko WJ, Hahm KB, Leontiadis GI, Ford AC, Ichinose M, Sugano K, Jeong M, Park JM, Han YM, Park KY, Lee DH, Yoo JH, Cho JY, Hahm KB, Bang CS, Baik GH, Shin IS, Kim JB, Suk KT, Yoon JH, Kim YS, Kim DJ * Helicobacter pylori Eradication for Prevention of Metachronous Recurrence after Endoscopic Resection of Early Gastric Cancer(238 visite) N Engl J Med (ISSN: 0028-4793, 0028-4793linking, 1533-4406electronic), 2015 Jun; 30642104201566393291: 749-756. Impact Factor:59.558 DettagliEsporta in BibTeXEsporta in EndNote
Aloj L, Aurilio M, Rinaldi V, D'Ambrosio L, Tesauro D, Peitl PK, Maina T, Mansi R, Von Guggenberg E, Joosten L, Sosabowski JK, Breeman WA, De Blois E, Koelewijn S, Melis M, Waser B, Beetschen K, Reubi JC, De Jong M * The EEE project(390 visite) Proc Int Cosm Ray Conf Icrc Universidad Nacional Autonoma De Mexico, 2007; 5(HEPART2): 977-980. Impact Factor:0 DettagliEsporta in BibTeXEsporta in EndNote
Vitiello M, Finamore E, Falanga A, Raieta K, Cantisani M, Galdiero F, Pedone C, Galdiero M, Galdiero S * Fusion in Coq(417 visite) Lecture Notes In Computer Science (ISSN: 0302-9743, 0302-974335404636319783540463634, 0302-974335402975459783540297543), 2001; 2178LNCS: 583-596. Impact Factor:0.415 DettagliEsporta in BibTeXEsporta in EndNote
Testino G, Leone S, Fagoonee S, Del Bas JM, Rodriguez B, Puiggros F, Marine S, Rodriguez MA, Morina D, Armengol L, Caimari A, Arola L, Cimini FA, Barchetta I, Carotti S, Bertoccini L, Baroni MG, Vespasiani-gentilucci U, Cavallo MG, Morini S, Nelson JE, Roth CL, Wilson LA, Yates KP, Aouizerat B, Morgan-stevenson V, Whalen E, Hoofnagle A, Mason M, Gersuk V, Yeh MM, Kowdley KV, Lee SM, Jun DW, Cho YK, Jang KS, Kucukazman M, Ata N, Dal K, Yeniova AO, Kefeli A, Basyigit S, Aktas B, Akin KO, Agladioglu K, Ure OS, Topal F, Nazligul Y, Beyan E, Ertugrul DT, Catena C, Cosma C, Camozzi V, Plebani M, Ermani M, Sechi LA, Fallo F, Goto Y, Ray MB, Mendenhall CL, French SW, Gartside PS Serum vitamin A deficiency and increased intrahepatic expression of cytokeratin antigen in alcoholic liver disease(467 visite) Hepatology (ISSN: 1827-1669electronic, 0026-4806linking), 1988 Sep; 83120693611123109(5): 1019-1026. Impact Factor:0.913 DettagliEsporta in BibTeXEsporta in EndNote
413 Records (395 escludendo Abstract e Conferenze). Impact factor totale: 1849.987 (1781.771 escludendo Abstract e Conferenze). Impact factor a 5 anni totale: 1832.339 (1755.271 escludendo Abstract e Conferenze).
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