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Ratiometric co-delivery of hydroxychloroquine and calculated low-dose paclitaxel efficiently suppresses tumor growth in hepatocellular carcinoma mouse models in vivo
Wang, Wenbin1,2; Sun, Hui2; Gong, Yan2; Liu, Xiangsheng3; Liu, Xiao4; Wang, Mengru1; Li, Silu1; Li, Jiulong2; Zhu, Lin1; Meng, Huan2
2022-06-01
发表期刊NANO TODAY
ISSN1748-0132
通讯作者Zhu, Lin(zhulin66zhulin@163.com) ; Meng, Huan(mengh@nanoctr.cn)
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.
关键词Ratiometric co-delivery Autophagy Hepatocellular carcinoma Chemo-immunotherapy Hydroxychloroquine Paclitaxel
DOI10.1016/j.nantod.2022.101446
关键词[WOS]HUMAN PANCREATIC-CANCER ; AUTOPHAGY ; GEMCITABINE
收录类别SCI
语种英语
资助项目National Center for Nanoscience and Technology, Chinese Academy of Sciences (CAS)[E1763911]
项目资助者National Center for Nanoscience and Technology, Chinese Academy of Sciences (CAS)
WOS研究方向Chemistry ; Science & Technology - Other Topics ; Materials Science
WOS类目Chemistry, Multidisciplinary ; Nanoscience & Nanotechnology ; Materials Science, Multidisciplinary
WOS记录号WOS:000788719300003
出版者ELSEVIER SCI LTD
引用统计
被引频次:5[WOS]   [WOS记录]     [WOS相关记录]
文献类型期刊论文
条目标识符http://ir.hfcas.ac.cn:8080/handle/334002/131501
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).
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