Ratiometric co-delivery of hydroxychloroquine and calculated low-dose paclitaxel efficiently suppresses tumor growth in hepatocellular carcinoma mouse models in vivo

doi:10.1016/j.nantod.2022.101446

	Ratiometric co-delivery of hydroxychloroquine and calculated low-dose paclitaxel efficiently suppresses tumor growth in hepatocellular carcinoma mouse models in vivo
	Wang, Wenbin 1,2; Sun, Hui 2; Gong, Yan 2; Liu, Xiangsheng 3; Liu, Xiao 4; Wang, Mengru 1; Li, Silu 1; Li, Jiulong 2; Zhu, Lin 1; Meng, Huan 2
刊名	NANO TODAY
	2022-06-01
卷号	44
关键词	Ratiometric co-delivery Autophagy Hepatocellular carcinoma Chemo-immunotherapy Hydroxychloroquine Paclitaxel
ISSN号	1748-0132
DOI	10.1016/j.nantod.2022.101446
通讯作者	Zhu, Lin(zhulin66zhulin@163.com) ; Meng, Huan(mengh@nanoctr.cn)
英文摘要	Utilizing a liposomal nanocarrier to co-encapsulate autophagy inhibitor hydroxychloroquine (HCQ) plus a calculated low-dose chemotherapeutic agent paclitaxel (PTX), we demonstrated a ratiometrically designed nanoformulation with synergistic anti-cancer efficacy in various hepatocellular carcinoma (HCC) mouse models. Using CompuSyn software to calculate drug synergy, we determined the synergistic drug ratios in cultured HCC cells, which became the reference to design ratiometric liposomes. Particle synthesis was accomplished by a film dispersion method for the calculated amount of PTX lipid incorporation and a remote loading process for HCQ import using ammonium sulfate. Ratiometric co-delivery led to synergistic killing effect and autophagy inhibition in cultured HCC cells and nude mice that were used to grow subcutaneous human HepG2 xenografts. Intravenous injection of ratiometric liposome yielded the most effective tumor shrinkage compared to various controls, including the free drug mix. A similar outcome was achieved in a HepG2 orthotopic model. We further explored the anti-cancer effect in a Hep1-6 murine HCC in immunocompetent mice, with or without co-administrated anti-PD1 antibody. Anti-PD1 antibody synergized with HCQ/PTX ratiometric liposome in the immunocompetent model.(c) 2022 Elsevier Ltd. All rights reserved.
资助项目	National Center for Nanoscience and Technology, Chinese Academy of Sciences (CAS)[E1763911]
WOS关键词	HUMAN PANCREATIC-CANCER ; AUTOPHAGY ; GEMCITABINE
WOS研究方向	Chemistry ; Science & Technology - Other Topics ; Materials Science
语种	英语
出版者	ELSEVIER SCI LTD
WOS记录号	WOS:000788719300003
资助机构	National Center for Nanoscience and Technology, Chinese Academy of Sciences (CAS)
内容类型	期刊论文
源URL	[http://ir.hfcas.ac.cn:8080/handle/334002/131500]
专题	中国科学院合肥物质科学研究院
通讯作者	Zhu, Lin; Meng, Huan
作者单位	1.Zhengzhou Univ, Affiliated Hosp 1, Dept Pharm, Zhengzhou 450052, Henan, Peoples R China 2.CAS Ctr Excellence Nanosci, Natl Ctr Nanosci & Technol, CAS Key Lab Biomed Effects Nanomat & Nanosafety, Beijing 100190, Peoples R China 3.Chinese Acad Sci, Univ Chinese Acad Sci, Canc Hosp, Zhejiang Canc Hosp,Inst Basic Med & Canc IBMC, Hangzhou 310022, Zhejiang, Peoples R China 4.Chinese Acad Med Sci, Beijing Hosp, Natl Ctr Gerontol, Inst Geriatr Med,Dept Gastroenterol, Beijing 100730, Peoples R China
推荐引用方式 GB/T 7714	Wang, Wenbin,Sun, Hui,Gong, Yan,et al. Ratiometric co-delivery of hydroxychloroquine and calculated low-dose paclitaxel efficiently suppresses tumor growth in hepatocellular carcinoma mouse models in vivo[J]. NANO TODAY,2022,44.
APA	Wang, Wenbin.,Sun, Hui.,Gong, Yan.,Liu, Xiangsheng.,Liu, Xiao.,...&Meng, Huan.(2022).Ratiometric co-delivery of hydroxychloroquine and calculated low-dose paclitaxel efficiently suppresses tumor growth in hepatocellular carcinoma mouse models in vivo.NANO TODAY,44.
MLA	Wang, Wenbin,et al."Ratiometric co-delivery of hydroxychloroquine and calculated low-dose paclitaxel efficiently suppresses tumor growth in hepatocellular carcinoma mouse models in vivo".NANO TODAY 44(2022).