99mTc Radiolabeled HA/TPGS-Based Curcumin-Loaded Nanoparticle for Breast Cancer Synergistic Theranostics: Design, in vitro and in vivo Evaluation

Chong Huang,1,2 Fen Chen,3,4 Ling Zhang,5 Yue Yang,2 Xinggang Yang,2 Weisan Pan2 1School of Traditional Chinese Medicine, Shenyang Pharmaceutical University, Shenyang 110016, People’s Republic of China; 2School of Pharmacy, Shenyang Pharmaceutical University, Shenyang 110016, People&rs...

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Autores principales:	Huang C, Chen F, Zhang L, Yang Y, Yang X, Pan W
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2020
Materias:	curcumin hyaluronan nanoparticle cancer theranostics Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/5a342ae33e79408180586629fdd7b771
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spelling	oai:doaj.org-article:5a342ae33e79408180586629fdd7b7712021-12-02T09:05:22Z99mTc Radiolabeled HA/TPGS-Based Curcumin-Loaded Nanoparticle for Breast Cancer Synergistic Theranostics: Design, in vitro and in vivo Evaluation1178-2013https://doaj.org/article/5a342ae33e79408180586629fdd7b7712020-04-01T00:00:00Zhttps://www.dovepress.com/99mtc-radiolabeled-hatpgs-based-curcumin-loaded-nanoparticle-for-breas-peer-reviewed-article-IJNhttps://doaj.org/toc/1178-2013Chong Huang,1,2 Fen Chen,3,4 Ling Zhang,5 Yue Yang,2 Xinggang Yang,2 Weisan Pan2 1School of Traditional Chinese Medicine, Shenyang Pharmaceutical University, Shenyang 110016, People’s Republic of China; 2School of Pharmacy, Shenyang Pharmaceutical University, Shenyang 110016, People’s Republic of China; 3Key Laboratory of Ministry of Education for TCM Viscera-State Theory and Applications, Liaoning University of Traditional Chinese Medicine, Shenyang 110847, People’s Republic of China; 4Zhejiang Jingxin Pharmaceutical Co., Ltd, Xinchang 312500, People’s Republic of China; 5Department of Biotherapy, Cancer Research Institute, The First Affiliated Hospital of China Medical University, Shenyang 110001, People’s Republic of ChinaCorrespondence: Weisan PanSchool of Pharmacy, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenyang 110016, People’s Republic of ChinaTel +86 24 2398 6313Email pppwwwsss@163.comFen ChenKey Laboratory of Ministry of Education for TCM Viscera-State Theory and Applications, Liaoning University of Traditional Chinese Medicine, 79 Chongshan East Road, Shenyang 110847, People’s Republic of ChinaTel +86 24 3120 7125Email chenfen1121@163.comBackground: Emerging cancer therapy requires highly sensitive diagnosis in combination with cancer-targeting therapy. In this study, a self-assembled pH-sensitive curcumin (Cur)-loaded nanoparticle of 99mTc radiolabeled hyaluronan-cholesteryl hemisuccinate conjugates (HA-CHEMS) and D-a-tocopheryl polyethylene glycol succinate (TPGS) was prepared for breast cancer synergistic theranostics.Materials and Methods: The synthesized amphiphilic HA-CHEMS conjugates and TPGS self-assembled into Cur-loaded nanoparticles (HA-CHEMS-Cur-TPGS NPs) in an aqueous environment. The physicochemical properties of HA-CHEMS-Cur-TPGS NPs were characterized by transmission electron microscopy (TEM) and dynamic lighter scattering (DLS). The in vitro cytotoxicity of HA-CHEMS-Cur-TPGS NPs against breast cancer cells was evaluated by using the methyl thiazolyl tetrazolium (MTT) assay. Moreover, the in vivo animal experiments of HA-CHEMS-Cur-TPGS NPs including SPECT/CT imaging biodistribution and antitumor efficiency were investigated in 4T1 tumor-bearing BALB/c mice; furthermore, pharmacokinetics were investigated in healthy mice.Results: HA-CHEMS-Cur-TPGS NPs exhibited high curcumin loading, uniform particle size distribution, and excellent stability in vitro. In the cytotoxicity assay, HA-CHEMS-Cur-TPGS NPs showed remarkably higher cytotoxicity to 4T1 cells with an IC50 value at 38 μg/mL, compared with free curcumin (77 μg/mL). Moreover, HA-CHEMS-Cur-TPGS NPs could be effectively and stably radiolabeled with 99mTc. The SPECT images showed that 99mTc-HA-CHEMS-Cur-TPGS NPs could target the 4T1 tumor up to 4.85± 0.24%ID/g at 4 h post-injection in BALB/c mice. More importantly, the in vivo antitumor efficacy studies showed that HA-CHEMS-Cur-TPGS NPs greatly inhibited the tumor growth without resulting in obvious toxicities to major organs.Conclusion: The results indicated that HA-CHEMS-Cur-TPGS NPs with stable 99mTc labeling and high curcumin-loading capacity hold great potential for breast cancer synergistic theranostics.Keywords: curcumin, hyaluronan, nanoparticle, cancer theranosticsHuang CChen FZhang LYang YYang XPan WDove Medical Pressarticlecurcuminhyaluronannanoparticlecancer theranosticsMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol Volume 15, Pp 2987-2998 (2020)
institution	DOAJ
collection	DOAJ
language	EN
topic	curcumin hyaluronan nanoparticle cancer theranostics Medicine (General) R5-920
spellingShingle	curcumin hyaluronan nanoparticle cancer theranostics Medicine (General) R5-920 Huang C Chen F Zhang L Yang Y Yang X Pan W 99mTc Radiolabeled HA/TPGS-Based Curcumin-Loaded Nanoparticle for Breast Cancer Synergistic Theranostics: Design, in vitro and in vivo Evaluation
description	Chong Huang,1,2 Fen Chen,3,4 Ling Zhang,5 Yue Yang,2 Xinggang Yang,2 Weisan Pan2 1School of Traditional Chinese Medicine, Shenyang Pharmaceutical University, Shenyang 110016, People’s Republic of China; 2School of Pharmacy, Shenyang Pharmaceutical University, Shenyang 110016, People’s Republic of China; 3Key Laboratory of Ministry of Education for TCM Viscera-State Theory and Applications, Liaoning University of Traditional Chinese Medicine, Shenyang 110847, People’s Republic of China; 4Zhejiang Jingxin Pharmaceutical Co., Ltd, Xinchang 312500, People’s Republic of China; 5Department of Biotherapy, Cancer Research Institute, The First Affiliated Hospital of China Medical University, Shenyang 110001, People’s Republic of ChinaCorrespondence: Weisan PanSchool of Pharmacy, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenyang 110016, People’s Republic of ChinaTel +86 24 2398 6313Email pppwwwsss@163.comFen ChenKey Laboratory of Ministry of Education for TCM Viscera-State Theory and Applications, Liaoning University of Traditional Chinese Medicine, 79 Chongshan East Road, Shenyang 110847, People’s Republic of ChinaTel +86 24 3120 7125Email chenfen1121@163.comBackground: Emerging cancer therapy requires highly sensitive diagnosis in combination with cancer-targeting therapy. In this study, a self-assembled pH-sensitive curcumin (Cur)-loaded nanoparticle of 99mTc radiolabeled hyaluronan-cholesteryl hemisuccinate conjugates (HA-CHEMS) and D-a-tocopheryl polyethylene glycol succinate (TPGS) was prepared for breast cancer synergistic theranostics.Materials and Methods: The synthesized amphiphilic HA-CHEMS conjugates and TPGS self-assembled into Cur-loaded nanoparticles (HA-CHEMS-Cur-TPGS NPs) in an aqueous environment. The physicochemical properties of HA-CHEMS-Cur-TPGS NPs were characterized by transmission electron microscopy (TEM) and dynamic lighter scattering (DLS). The in vitro cytotoxicity of HA-CHEMS-Cur-TPGS NPs against breast cancer cells was evaluated by using the methyl thiazolyl tetrazolium (MTT) assay. Moreover, the in vivo animal experiments of HA-CHEMS-Cur-TPGS NPs including SPECT/CT imaging biodistribution and antitumor efficiency were investigated in 4T1 tumor-bearing BALB/c mice; furthermore, pharmacokinetics were investigated in healthy mice.Results: HA-CHEMS-Cur-TPGS NPs exhibited high curcumin loading, uniform particle size distribution, and excellent stability in vitro. In the cytotoxicity assay, HA-CHEMS-Cur-TPGS NPs showed remarkably higher cytotoxicity to 4T1 cells with an IC50 value at 38 μg/mL, compared with free curcumin (77 μg/mL). Moreover, HA-CHEMS-Cur-TPGS NPs could be effectively and stably radiolabeled with 99mTc. The SPECT images showed that 99mTc-HA-CHEMS-Cur-TPGS NPs could target the 4T1 tumor up to 4.85± 0.24%ID/g at 4 h post-injection in BALB/c mice. More importantly, the in vivo antitumor efficacy studies showed that HA-CHEMS-Cur-TPGS NPs greatly inhibited the tumor growth without resulting in obvious toxicities to major organs.Conclusion: The results indicated that HA-CHEMS-Cur-TPGS NPs with stable 99mTc labeling and high curcumin-loading capacity hold great potential for breast cancer synergistic theranostics.Keywords: curcumin, hyaluronan, nanoparticle, cancer theranostics
format	article
author	Huang C Chen F Zhang L Yang Y Yang X Pan W
author_facet	Huang C Chen F Zhang L Yang Y Yang X Pan W
author_sort	Huang C
title	99mTc Radiolabeled HA/TPGS-Based Curcumin-Loaded Nanoparticle for Breast Cancer Synergistic Theranostics: Design, in vitro and in vivo Evaluation
title_short	99mTc Radiolabeled HA/TPGS-Based Curcumin-Loaded Nanoparticle for Breast Cancer Synergistic Theranostics: Design, in vitro and in vivo Evaluation
title_full	99mTc Radiolabeled HA/TPGS-Based Curcumin-Loaded Nanoparticle for Breast Cancer Synergistic Theranostics: Design, in vitro and in vivo Evaluation
title_fullStr	99mTc Radiolabeled HA/TPGS-Based Curcumin-Loaded Nanoparticle for Breast Cancer Synergistic Theranostics: Design, in vitro and in vivo Evaluation
title_full_unstemmed	99mTc Radiolabeled HA/TPGS-Based Curcumin-Loaded Nanoparticle for Breast Cancer Synergistic Theranostics: Design, in vitro and in vivo Evaluation
title_sort	99mtc radiolabeled ha/tpgs-based curcumin-loaded nanoparticle for breast cancer synergistic theranostics: design, in vitro and in vivo evaluation
publisher	Dove Medical Press
publishDate	2020
url	https://doaj.org/article/5a342ae33e79408180586629fdd7b771
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_version_	1718398245587124224

99mTc Radiolabeled HA/TPGS-Based Curcumin-Loaded Nanoparticle for Breast Cancer Synergistic Theranostics: Design, in vitro and in vivo Evaluation

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