Functionalized milk-protein-coated magnetic nanoparticles for MRI-monitored targeted therapy of pancreatic cancer

Jing Huang,1,2 Weiping Qian,3 Liya Wang,1,2 Hui Wu,1 Hongyu Zhou,3 Andrew Yongqiang Wang,4 Hongbo Chen,5 Lily Yang,3 Hui Mao1,2 1Department of Radiology and Imaging Sciences, 2Center for Systems Imaging, 3Department of Surgery, Emory University School of Medicine, Atlanta, GA, USA; 4Ocean Nanotech...

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Autores principales:	Huang J, Qian W, Wang L, Wu H, Zhou H, Wang AY, Chen H, Yang L, Mao H
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2016
Materias:	active targeting drug delivery cisplatin magnetic nanoparticles magnetic resonance imaging pancreatic cancer. Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/f661f38436514d928087962d45f3b13f
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spelling	oai:doaj.org-article:f661f38436514d928087962d45f3b13f2021-12-02T02:01:52ZFunctionalized milk-protein-coated magnetic nanoparticles for MRI-monitored targeted therapy of pancreatic cancer1178-2013https://doaj.org/article/f661f38436514d928087962d45f3b13f2016-07-01T00:00:00Zhttps://www.dovepress.com/functionalized-milk-protein-coated-magnetic-nanoparticles-for-mri-moni-peer-reviewed-article-IJNhttps://doaj.org/toc/1178-2013Jing Huang,1,2 Weiping Qian,3 Liya Wang,1,2 Hui Wu,1 Hongyu Zhou,3 Andrew Yongqiang Wang,4 Hongbo Chen,5 Lily Yang,3 Hui Mao1,2 1Department of Radiology and Imaging Sciences, 2Center for Systems Imaging, 3Department of Surgery, Emory University School of Medicine, Atlanta, GA, USA; 4Ocean Nanotech LLC, Springdale, AR, USA; 5School of Life and Environmental Sciences, Guilin University of Electronic Technology, Guilin, Guangxi, People’s Republic of China Abstract: Engineered nanocarriers have emerged as a promising platform for cancer therapy. However, the therapeutic efficacy is limited by low drug loading efficiency, poor passive targeting to tumors, and severe systemic side effects. Herein, we report a new class of nanoconstructs based on milk protein (casein)-coated magnetic iron oxide (CNIO) nanoparticles for targeted and image-guided pancreatic cancer treatment. The tumor-targeting amino-terminal fragment (ATF) of urokinase plasminogen activator and the antitumor drug cisplatin (CDDP) were engineered on this nanoplatform. High drug loading (~25 wt%) and sustained release at physiological conditions were achieved through the exchange and encapsulation strategy. These ATF-CNIO-CDDP nanoparticles demonstrated actively targeted delivery of CDDP to orthotopic pancreatic tumors in mice. The effective accumulation and distribution of ATF-CNIO-CDDP was evidenced by magnetic resonance imaging, based on the T2-weighted contrast resulting from the specific accumulation of ATF-CNIO-CDDP in the tumor. Actively targeted delivery of ATF-CNIO-CDDP led to improved therapeutic efficacy in comparison with free CDDP and nontargeted CNIO-CDDP treatment. Meanwhile, less systemic side effects were observed in the nanocarrier-treated groups than that in the group treated with free CDDP. Hematoxylin and Eosin and Sirius Red staining of tumor sections revealed the possible disruption of stroma during the treatment with ATF-CNIO-CDDP. Overall, our results suggest that ATF-CNIO-CDDP can be an effective theranostic platform for active targeting-enhanced and image-guided cancer treatment while simultaneously reducing the systemic toxicity. Keywords: active targeting, drug delivery, cisplatin, magnetic nanoparticles, magnetic resonance imaging, pancreatic cancerHuang JQian WWang LWu HZhou HWang AYChen HYang LMao HDove Medical Pressarticleactive targetingdrug deliverycisplatinmagnetic nanoparticlesmagnetic resonance imagingpancreatic cancer.Medicine (General)R5-920ENInternational Journal of Nanomedicine, Vol 2016, Iss default, Pp 3087-3099 (2016)
institution	DOAJ
collection	DOAJ
language	EN
topic	active targeting drug delivery cisplatin magnetic nanoparticles magnetic resonance imaging pancreatic cancer. Medicine (General) R5-920
spellingShingle	active targeting drug delivery cisplatin magnetic nanoparticles magnetic resonance imaging pancreatic cancer. Medicine (General) R5-920 Huang J Qian W Wang L Wu H Zhou H Wang AY Chen H Yang L Mao H Functionalized milk-protein-coated magnetic nanoparticles for MRI-monitored targeted therapy of pancreatic cancer
description	Jing Huang,1,2 Weiping Qian,3 Liya Wang,1,2 Hui Wu,1 Hongyu Zhou,3 Andrew Yongqiang Wang,4 Hongbo Chen,5 Lily Yang,3 Hui Mao1,2 1Department of Radiology and Imaging Sciences, 2Center for Systems Imaging, 3Department of Surgery, Emory University School of Medicine, Atlanta, GA, USA; 4Ocean Nanotech LLC, Springdale, AR, USA; 5School of Life and Environmental Sciences, Guilin University of Electronic Technology, Guilin, Guangxi, People’s Republic of China Abstract: Engineered nanocarriers have emerged as a promising platform for cancer therapy. However, the therapeutic efficacy is limited by low drug loading efficiency, poor passive targeting to tumors, and severe systemic side effects. Herein, we report a new class of nanoconstructs based on milk protein (casein)-coated magnetic iron oxide (CNIO) nanoparticles for targeted and image-guided pancreatic cancer treatment. The tumor-targeting amino-terminal fragment (ATF) of urokinase plasminogen activator and the antitumor drug cisplatin (CDDP) were engineered on this nanoplatform. High drug loading (~25 wt%) and sustained release at physiological conditions were achieved through the exchange and encapsulation strategy. These ATF-CNIO-CDDP nanoparticles demonstrated actively targeted delivery of CDDP to orthotopic pancreatic tumors in mice. The effective accumulation and distribution of ATF-CNIO-CDDP was evidenced by magnetic resonance imaging, based on the T2-weighted contrast resulting from the specific accumulation of ATF-CNIO-CDDP in the tumor. Actively targeted delivery of ATF-CNIO-CDDP led to improved therapeutic efficacy in comparison with free CDDP and nontargeted CNIO-CDDP treatment. Meanwhile, less systemic side effects were observed in the nanocarrier-treated groups than that in the group treated with free CDDP. Hematoxylin and Eosin and Sirius Red staining of tumor sections revealed the possible disruption of stroma during the treatment with ATF-CNIO-CDDP. Overall, our results suggest that ATF-CNIO-CDDP can be an effective theranostic platform for active targeting-enhanced and image-guided cancer treatment while simultaneously reducing the systemic toxicity. Keywords: active targeting, drug delivery, cisplatin, magnetic nanoparticles, magnetic resonance imaging, pancreatic cancer
format	article
author	Huang J Qian W Wang L Wu H Zhou H Wang AY Chen H Yang L Mao H
author_facet	Huang J Qian W Wang L Wu H Zhou H Wang AY Chen H Yang L Mao H
author_sort	Huang J
title	Functionalized milk-protein-coated magnetic nanoparticles for MRI-monitored targeted therapy of pancreatic cancer
title_short	Functionalized milk-protein-coated magnetic nanoparticles for MRI-monitored targeted therapy of pancreatic cancer
title_full	Functionalized milk-protein-coated magnetic nanoparticles for MRI-monitored targeted therapy of pancreatic cancer
title_fullStr	Functionalized milk-protein-coated magnetic nanoparticles for MRI-monitored targeted therapy of pancreatic cancer
title_full_unstemmed	Functionalized milk-protein-coated magnetic nanoparticles for MRI-monitored targeted therapy of pancreatic cancer
title_sort	functionalized milk-protein-coated magnetic nanoparticles for mri-monitored targeted therapy of pancreatic cancer
publisher	Dove Medical Press
publishDate	2016
url	https://doaj.org/article/f661f38436514d928087962d45f3b13f
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_version_	1718402811040890880

Functionalized milk-protein-coated magnetic nanoparticles for MRI-monitored targeted therapy of pancreatic cancer

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