Ag/Au Bimetallic Nanoparticles Inhibit Tumor Growth and Prevent Metastasis in a Mouse Model

Hector Katifelis,1 Iuliia Mukha,2 Penelope Bouziotis,3 Nadiia Vityuk,2 Charalampos Tsoukalas,3 Andreas C Lazaris,4 Anna Lyberopoulou,1 George E Theodoropoulos,5 Efstathios P Efstathopoulos,6 Maria Gazouli1,6 1Laboratory of Biology, Medical School, National and Kapodistrian University of Athens, Athe...

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Autores principales:	Katifelis H, Mukha I, Bouziotis P, Vityuk N, Tsoukalas C, Lazaris AC, Lyberopoulou A, Theodoropoulos GE, Efstathopoulos EP, Gazouli M
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2020
Materias:	nanoparticles cancer scid mice trail casp-3 Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/be83a7edad9c4aa5995a2e1527a010b7
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spelling	oai:doaj.org-article:be83a7edad9c4aa5995a2e1527a010b72021-12-02T03:57:59ZAg/Au Bimetallic Nanoparticles Inhibit Tumor Growth and Prevent Metastasis in a Mouse Model1178-2013https://doaj.org/article/be83a7edad9c4aa5995a2e1527a010b72020-08-01T00:00:00Zhttps://www.dovepress.com/agau-bimetallic-nanoparticles-inhibit-tumor-growth-and-prevent-metasta-peer-reviewed-article-IJNhttps://doaj.org/toc/1178-2013Hector Katifelis,1 Iuliia Mukha,2 Penelope Bouziotis,3 Nadiia Vityuk,2 Charalampos Tsoukalas,3 Andreas C Lazaris,4 Anna Lyberopoulou,1 George E Theodoropoulos,5 Efstathios P Efstathopoulos,6 Maria Gazouli1,6 1Laboratory of Biology, Medical School, National and Kapodistrian University of Athens, Athens, Greece; 2Chuiko Institute of Surface Chemistry, National Academy of Sciences of Ukraine, Kyiv, Ukraine; 3Radiochemical Studies Laboratory, Institute of Nuclear & Radiological Sciences & Technology, Energy & Safety, National Center for Scientific Research “Demokritos”, Athens, Greece; 4 1st Department of Pathology, National and Kapodistrian University of Athens, Athens, Greece; 5 1st Propaedeutic University Surgery Clinic, Hippocratio General Hospital, Medical School, National and Kapodistrian University of Athens, Athens, Greece; 6 2nd Department of Radiology, Medical School, National and Kapodistrian University of Athens, Athens, GreeceCorrespondence: Maria Gazouli Email mgazouli@med.uoa.grPurpose: To evaluate the antitumor efficacy of Ag3Au1Trp1:2NPs in a SCID mouse cancer model, with respect to their effect on tumor growth, on tumor’s metastatic potential and the underlying molecular mechanism.Subjects and Methods: Ag3Au1Trp1:2NPs were radiolabeled with Gallium-68 and the biodistribution was studied in Swiss mice without tumors and in SCID mice bearing tumors. SCID mice received intratumoral Ag3Au1Trp1:2NPs and tumor size was measured using calipers. Lung and liver tissues were extracted and studied microscopically for the detection of any metastatic sites. Changes in the Caspase-3 and TNF-related apoptosis-inducing ligand (TRAIL) were also investigated using real-time PCR and Western blot techniques, respectively.Results: In the 4T1 tumor-bearing SCID mice, Ag3Au1Trp1:2NPs showed quick passive accumulation at tumor sites at 30 mins post-injection. Mice that received the highest dose of NPs (5.6mg/mL) demonstrated a 1.9-fold lower tumor volume compared to that of the control group at 11 days post-injection, while mice that did not receive NPs showed metastatic sites in liver and lung. Extracted tumor tissue of treated mice revealed increased Casp-3 mRNA levels as well as elevated TRAIL protein levels.Conclusion: Based on our results, Ag3Au1Trp1:2NPs express anti-tumor and anti-metastatic effects in vivo. Ag3Au1Trp1:2NPs also reach tumor site via the enhancement and retention effect which results in the apoptotic death of cancerous cells selectively via the extrinsic TRAIL-dependent pathway.Keywords: nanoparticles, cancer, SCID mice, TRAIL, Casp-3Katifelis HMukha IBouziotis PVityuk NTsoukalas CLazaris ACLyberopoulou ATheodoropoulos GEEfstathopoulos EPGazouli MDove Medical Pressarticlenanoparticlescancerscid micetrailcasp-3Medicine (General)R5-920ENInternational Journal of Nanomedicine, Vol Volume 15, Pp 6019-6032 (2020)
institution	DOAJ
collection	DOAJ
language	EN
topic	nanoparticles cancer scid mice trail casp-3 Medicine (General) R5-920
spellingShingle	nanoparticles cancer scid mice trail casp-3 Medicine (General) R5-920 Katifelis H Mukha I Bouziotis P Vityuk N Tsoukalas C Lazaris AC Lyberopoulou A Theodoropoulos GE Efstathopoulos EP Gazouli M Ag/Au Bimetallic Nanoparticles Inhibit Tumor Growth and Prevent Metastasis in a Mouse Model
description	Hector Katifelis,1 Iuliia Mukha,2 Penelope Bouziotis,3 Nadiia Vityuk,2 Charalampos Tsoukalas,3 Andreas C Lazaris,4 Anna Lyberopoulou,1 George E Theodoropoulos,5 Efstathios P Efstathopoulos,6 Maria Gazouli1,6 1Laboratory of Biology, Medical School, National and Kapodistrian University of Athens, Athens, Greece; 2Chuiko Institute of Surface Chemistry, National Academy of Sciences of Ukraine, Kyiv, Ukraine; 3Radiochemical Studies Laboratory, Institute of Nuclear & Radiological Sciences & Technology, Energy & Safety, National Center for Scientific Research “Demokritos”, Athens, Greece; 4 1st Department of Pathology, National and Kapodistrian University of Athens, Athens, Greece; 5 1st Propaedeutic University Surgery Clinic, Hippocratio General Hospital, Medical School, National and Kapodistrian University of Athens, Athens, Greece; 6 2nd Department of Radiology, Medical School, National and Kapodistrian University of Athens, Athens, GreeceCorrespondence: Maria Gazouli Email mgazouli@med.uoa.grPurpose: To evaluate the antitumor efficacy of Ag3Au1Trp1:2NPs in a SCID mouse cancer model, with respect to their effect on tumor growth, on tumor’s metastatic potential and the underlying molecular mechanism.Subjects and Methods: Ag3Au1Trp1:2NPs were radiolabeled with Gallium-68 and the biodistribution was studied in Swiss mice without tumors and in SCID mice bearing tumors. SCID mice received intratumoral Ag3Au1Trp1:2NPs and tumor size was measured using calipers. Lung and liver tissues were extracted and studied microscopically for the detection of any metastatic sites. Changes in the Caspase-3 and TNF-related apoptosis-inducing ligand (TRAIL) were also investigated using real-time PCR and Western blot techniques, respectively.Results: In the 4T1 tumor-bearing SCID mice, Ag3Au1Trp1:2NPs showed quick passive accumulation at tumor sites at 30 mins post-injection. Mice that received the highest dose of NPs (5.6mg/mL) demonstrated a 1.9-fold lower tumor volume compared to that of the control group at 11 days post-injection, while mice that did not receive NPs showed metastatic sites in liver and lung. Extracted tumor tissue of treated mice revealed increased Casp-3 mRNA levels as well as elevated TRAIL protein levels.Conclusion: Based on our results, Ag3Au1Trp1:2NPs express anti-tumor and anti-metastatic effects in vivo. Ag3Au1Trp1:2NPs also reach tumor site via the enhancement and retention effect which results in the apoptotic death of cancerous cells selectively via the extrinsic TRAIL-dependent pathway.Keywords: nanoparticles, cancer, SCID mice, TRAIL, Casp-3
format	article
author	Katifelis H Mukha I Bouziotis P Vityuk N Tsoukalas C Lazaris AC Lyberopoulou A Theodoropoulos GE Efstathopoulos EP Gazouli M
author_facet	Katifelis H Mukha I Bouziotis P Vityuk N Tsoukalas C Lazaris AC Lyberopoulou A Theodoropoulos GE Efstathopoulos EP Gazouli M
author_sort	Katifelis H
title	Ag/Au Bimetallic Nanoparticles Inhibit Tumor Growth and Prevent Metastasis in a Mouse Model
title_short	Ag/Au Bimetallic Nanoparticles Inhibit Tumor Growth and Prevent Metastasis in a Mouse Model
title_full	Ag/Au Bimetallic Nanoparticles Inhibit Tumor Growth and Prevent Metastasis in a Mouse Model
title_fullStr	Ag/Au Bimetallic Nanoparticles Inhibit Tumor Growth and Prevent Metastasis in a Mouse Model
title_full_unstemmed	Ag/Au Bimetallic Nanoparticles Inhibit Tumor Growth and Prevent Metastasis in a Mouse Model
title_sort	ag/au bimetallic nanoparticles inhibit tumor growth and prevent metastasis in a mouse model
publisher	Dove Medical Press
publishDate	2020
url	https://doaj.org/article/be83a7edad9c4aa5995a2e1527a010b7
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Ag/Au Bimetallic Nanoparticles Inhibit Tumor Growth and Prevent Metastasis in a Mouse Model

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