Successful in vivo hyperthermal therapy toward breast cancer by Chinese medicine shikonin-loaded thermosensitive micelle

Yonghua Su,1,* Nian Huang,1,* Di Chen,2,* Li Zhang,2,* Xia Dong,2 Yun Sun,2 Xiandi Zhu,2 Fulei Zhang,2 Jie Gao,2 Ying Wang,2 Kexing Fan,2 Puichi Lo,3 Wei Li,2 Changquan Ling1 1Department of Integrative Oncology, Changhai Hospital of Traditional Chinese Medicine, 2International Joint Cancer Institut...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Su Y, Huang N, Chen D, Zhang L, Dong X, Sun Y, Zhu X, Zhang F, Gao J, Wang Y, Fan K, Lo P, Li W, Ling CQ
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2017
Materias:	Thermosensitive micelle Shikonin Breast cancer Intra-tumor accumulation Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/1a3f2093f6d3476f9830ac0a83dd48d5
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:1a3f2093f6d3476f9830ac0a83dd48d5
record_format	dspace
spelling	oai:doaj.org-article:1a3f2093f6d3476f9830ac0a83dd48d52021-12-02T00:59:55ZSuccessful in vivo hyperthermal therapy toward breast cancer by Chinese medicine shikonin-loaded thermosensitive micelle1178-2013https://doaj.org/article/1a3f2093f6d3476f9830ac0a83dd48d52017-05-01T00:00:00Zhttps://www.dovepress.com/successful-in-vivo-hyperthermal-therapy-toward-breast-cancer-by-chines-peer-reviewed-article-IJNhttps://doaj.org/toc/1178-2013Yonghua Su,1,* Nian Huang,1,* Di Chen,2,* Li Zhang,2,* Xia Dong,2 Yun Sun,2 Xiandi Zhu,2 Fulei Zhang,2 Jie Gao,2 Ying Wang,2 Kexing Fan,2 Puichi Lo,3 Wei Li,2 Changquan Ling1 1Department of Integrative Oncology, Changhai Hospital of Traditional Chinese Medicine, 2International Joint Cancer Institute, The Second Military Medical University, Shanghai, 3Department of Biomedical Sciences, City University of Hong Kong, Kowloon Tong, Hong Kong, China *These authors contributed equally to this work Abstract: The Chinese traditional medicine Shikonin is an ideal drug due to its multiple targets to tumor cells. But in clinics, improving its aqueous solubility and tumor accumulation is still a challenge. Herein, a copolymer with tunable poly(N-isopropylacrymaide) and polylactic acid block lengths is designed, synthesized, and characterized in nuclear magnetic resonance. The corresponding thermosensitive nanomicelle (TN) with well-defined core-shell structure is then assembled in an aqueous solution. For promoting the therapeutic index, the physical-chemistry properties of TNs including narrow size, low critical micellar concentration, high serum stability, tunable volume phase transition temperature (VPTT), high drug-loading capacity, and temperature-controlled drug release are systematically investigated and regulated through the fine self-assembly. The shikonin is then entrapped in a degradable inner core resulting in a shikonin-loaded thermosensitive nanomicelle (STN) with a VPTT of ~40°C. Compared with small-molecular shikonin, the in vitro cellular internalization and cytotoxicity of STN against breast cancer cells (Michigan Cancer Foundation-7) are obviously enhanced. In addition, the therapeutic effect is further enhanced by the programmed cell death (PCD) specifically evoked by shikonin. Interestingly, both the proliferation inhibition and PCD are synergistically promoted as T > VPTT, namely the temperature-regulated passive targeting. Consequently, as intravenous injection is administered to the BALB/c nude mice bearing breast cancer, the intra-tumor accumulation of STNs is significantly increased as T > VPTT, which is regulated by the in-house developed heating device. The in vivo antitumor assays against breast cancer further confirm the synergistically enhanced therapeutic efficiency. The findings of this study indicate that STN is a potential effective nanoformulation in clinical cancer therapy. Keywords: thermosensitive micelle, shikonin, breast cancer, intra-tumor accumulation, critical micelle concentration, hyperthermal therapy, in vivoSu YHuang NChen DZhang LDong XSun YZhu XZhang FGao JWang YFan KLo PLi WLing CQDove Medical PressarticleThermosensitive micelleShikoninBreast cancerIntra-tumor accumulationMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol Volume 12, Pp 4019-4035 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Thermosensitive micelle Shikonin Breast cancer Intra-tumor accumulation Medicine (General) R5-920
spellingShingle	Thermosensitive micelle Shikonin Breast cancer Intra-tumor accumulation Medicine (General) R5-920 Su Y Huang N Chen D Zhang L Dong X Sun Y Zhu X Zhang F Gao J Wang Y Fan K Lo P Li W Ling CQ Successful in vivo hyperthermal therapy toward breast cancer by Chinese medicine shikonin-loaded thermosensitive micelle
description	Yonghua Su,1,* Nian Huang,1,* Di Chen,2,* Li Zhang,2,* Xia Dong,2 Yun Sun,2 Xiandi Zhu,2 Fulei Zhang,2 Jie Gao,2 Ying Wang,2 Kexing Fan,2 Puichi Lo,3 Wei Li,2 Changquan Ling1 1Department of Integrative Oncology, Changhai Hospital of Traditional Chinese Medicine, 2International Joint Cancer Institute, The Second Military Medical University, Shanghai, 3Department of Biomedical Sciences, City University of Hong Kong, Kowloon Tong, Hong Kong, China *These authors contributed equally to this work Abstract: The Chinese traditional medicine Shikonin is an ideal drug due to its multiple targets to tumor cells. But in clinics, improving its aqueous solubility and tumor accumulation is still a challenge. Herein, a copolymer with tunable poly(N-isopropylacrymaide) and polylactic acid block lengths is designed, synthesized, and characterized in nuclear magnetic resonance. The corresponding thermosensitive nanomicelle (TN) with well-defined core-shell structure is then assembled in an aqueous solution. For promoting the therapeutic index, the physical-chemistry properties of TNs including narrow size, low critical micellar concentration, high serum stability, tunable volume phase transition temperature (VPTT), high drug-loading capacity, and temperature-controlled drug release are systematically investigated and regulated through the fine self-assembly. The shikonin is then entrapped in a degradable inner core resulting in a shikonin-loaded thermosensitive nanomicelle (STN) with a VPTT of ~40°C. Compared with small-molecular shikonin, the in vitro cellular internalization and cytotoxicity of STN against breast cancer cells (Michigan Cancer Foundation-7) are obviously enhanced. In addition, the therapeutic effect is further enhanced by the programmed cell death (PCD) specifically evoked by shikonin. Interestingly, both the proliferation inhibition and PCD are synergistically promoted as T > VPTT, namely the temperature-regulated passive targeting. Consequently, as intravenous injection is administered to the BALB/c nude mice bearing breast cancer, the intra-tumor accumulation of STNs is significantly increased as T > VPTT, which is regulated by the in-house developed heating device. The in vivo antitumor assays against breast cancer further confirm the synergistically enhanced therapeutic efficiency. The findings of this study indicate that STN is a potential effective nanoformulation in clinical cancer therapy. Keywords: thermosensitive micelle, shikonin, breast cancer, intra-tumor accumulation, critical micelle concentration, hyperthermal therapy, in vivo
format	article
author	Su Y Huang N Chen D Zhang L Dong X Sun Y Zhu X Zhang F Gao J Wang Y Fan K Lo P Li W Ling CQ
author_facet	Su Y Huang N Chen D Zhang L Dong X Sun Y Zhu X Zhang F Gao J Wang Y Fan K Lo P Li W Ling CQ
author_sort	Su Y
title	Successful in vivo hyperthermal therapy toward breast cancer by Chinese medicine shikonin-loaded thermosensitive micelle
title_short	Successful in vivo hyperthermal therapy toward breast cancer by Chinese medicine shikonin-loaded thermosensitive micelle
title_full	Successful in vivo hyperthermal therapy toward breast cancer by Chinese medicine shikonin-loaded thermosensitive micelle
title_fullStr	Successful in vivo hyperthermal therapy toward breast cancer by Chinese medicine shikonin-loaded thermosensitive micelle
title_full_unstemmed	Successful in vivo hyperthermal therapy toward breast cancer by Chinese medicine shikonin-loaded thermosensitive micelle
title_sort	successful in vivo hyperthermal therapy toward breast cancer by chinese medicine shikonin-loaded thermosensitive micelle
publisher	Dove Medical Press
publishDate	2017
url	https://doaj.org/article/1a3f2093f6d3476f9830ac0a83dd48d5
work_keys_str_mv	AT suy successfulinvivohyperthermaltherapytowardbreastcancerbychinesemedicineshikoninloadedthermosensitivemicelle AT huangn successfulinvivohyperthermaltherapytowardbreastcancerbychinesemedicineshikoninloadedthermosensitivemicelle AT chend successfulinvivohyperthermaltherapytowardbreastcancerbychinesemedicineshikoninloadedthermosensitivemicelle AT zhangl successfulinvivohyperthermaltherapytowardbreastcancerbychinesemedicineshikoninloadedthermosensitivemicelle AT dongx successfulinvivohyperthermaltherapytowardbreastcancerbychinesemedicineshikoninloadedthermosensitivemicelle AT suny successfulinvivohyperthermaltherapytowardbreastcancerbychinesemedicineshikoninloadedthermosensitivemicelle AT zhux successfulinvivohyperthermaltherapytowardbreastcancerbychinesemedicineshikoninloadedthermosensitivemicelle AT zhangf successfulinvivohyperthermaltherapytowardbreastcancerbychinesemedicineshikoninloadedthermosensitivemicelle AT gaoj successfulinvivohyperthermaltherapytowardbreastcancerbychinesemedicineshikoninloadedthermosensitivemicelle AT wangy successfulinvivohyperthermaltherapytowardbreastcancerbychinesemedicineshikoninloadedthermosensitivemicelle AT fank successfulinvivohyperthermaltherapytowardbreastcancerbychinesemedicineshikoninloadedthermosensitivemicelle AT lop successfulinvivohyperthermaltherapytowardbreastcancerbychinesemedicineshikoninloadedthermosensitivemicelle AT liw successfulinvivohyperthermaltherapytowardbreastcancerbychinesemedicineshikoninloadedthermosensitivemicelle AT lingcq successfulinvivohyperthermaltherapytowardbreastcancerbychinesemedicineshikoninloadedthermosensitivemicelle
_version_	1718403367580991488

Successful in vivo hyperthermal therapy toward breast cancer by Chinese medicine shikonin-loaded thermosensitive micelle

Ejemplares similares