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Prodrug nanoparticles rationally integrating stroma modification and chemotherapy to treat metastatic pancreatic cancer

文献类型：期刊论文

作者Wang, Liying1,2,3,10,11; Liu, Zimo2,3,10,11; Zhou, Quan2,3; Gu, Sufang2,3; Liu, Xiangsheng4; Huang, Jianxiang2,3; Jiang, Haiping5; Wang, Huifang2,3; Cao, Liping6; Sun, Jihong1
刊名BIOMATERIALS
出版日期2021-11-01
卷号278
关键词Pancreatic cancer Polymeric prodrug Calcipotriol Cancer-associated fibroblast Metastasis
ISSN号0142-9612
DOI10.1016/j.biomaterials.2021.121176
通讯作者Meng, Huan(mengh@nanoctr.cn) ; Liu, Xiangrui(xiangrui@zju.edu.cn)
英文摘要Accumulating evidence suggests that stromal modifications improve chemotherapeutic outcomes in pancreatic ductal adenocarcinoma (PDAC). However, combination regimens of stroma-modifying agents and smallmolecule cytotoxic drugs have achieved only limited improvements in the clinic, probably due to unsatisfactory pharmacokinetic profiles and restricted drug distribution in tumors. Here, we developed self-assembled prodrug nanoparticles integrating a stromal reprogramming inducer, calcipotriol (CAL), and a potent chemotherapeutic agent, 7-Ethyl-10-hydroxycamptothecin (SN38), to treat PDAC. While SN38 is conjugated to the block polymer backbone, CAL is loaded into the inner hydrophobic space during polymer self-assembly into nanoparticles. To achieve an efficient drug co-package, a planar and hydrophobic cholesterol domain was introduced to stabilize the hydrophobic CAL. Notably, the blood circulation time of CAL significantly improved as CAL|SN38 nanoparticle (CAL|SN38 NP). In addition, CAL|SN38 NP treatment significantly decreased the expression of N-cadherin, collagen, and fibronectin in tumors, which play critical roles in PDAC metastasis. Potent inhibition of primary tumor growth and vigorous anti-metastasis effects were observed after systemic administration of CAL|SN38 NP to stroma-rich PDAC orthotopic tumor-bearing mice. These findings provide a promising paradigm for developing tailor-made nanoparticles with potent stroma-modification capability to combat metastatic cancer.
WOS关键词STELLATE CELLS ; ACCUMULATION
WOS研究方向Engineering ; Materials Science
语种英语
WOS记录号WOS:000710782400001
出版者ELSEVIER SCI LTD
源URL[http://ir.hfcas.ac.cn:8080/handle/334002/125771]  
专题中国科学院合肥物质科学研究院
通讯作者Meng, Huan; Liu, Xiangrui
作者单位1.Zhejiang Univ, Sir Run Run Shaw Hosp, Dept Radiol, Sch Med, Hangzhou 310058, Peoples R China
2.Zhejiang Univ, Coll Chem & Biol Engn, Key Lab Biomass Chem Engn, Minist Educ, Hangzhou 310027, Peoples R China
3.Zhejiang Univ, Coll Chem & Biol Engn, Ctr Bionanoengn, Hangzhou 310027, Peoples R China
4.Chinese Acad Sci, Univ Chinese Acad Sci, Inst Basic Med & Canc IBMC, Canc Hosp, Hangzhou 310022, Zhejiang, Peoples R China
5.Zhejiang Univ, Dept Med Oncol, Affiliated Hosp 1, Med Sch, Hangzhou 310016, Peoples R China
6.Zhejiang Univ, Sir Run Run Shaw Hosp, Dept Gen Surg, Sch Med, Hangzhou 310016, Peoples R China
7.Natl Ctr Nanosci & Technol, CAS Key Lab Biomed Effects Nanomat & Nanosafety, Beijing 100190, Peoples R China
8.Zhejiang Univ, Canc Ctr, Hangzhou 310058, Peoples R China
9.Natl Ctr Nanosci & Technol, CAS Ctr Excellence Nanosci, Beijing 100190, Peoples R China
10.Zhejiang Univ, Dept Pharmacol, Sch Med, Affiliated Hosp 2, Hangzhou 310058, Peoples R China
推荐引用方式
GB/T 7714		 Wang, Liying,Liu, Zimo,Zhou, Quan,et al. Prodrug nanoparticles rationally integrating stroma modification and chemotherapy to treat metastatic pancreatic cancer[J]. BIOMATERIALS,2021,278.
APA Wang, Liying.,Liu, Zimo.,Zhou, Quan.,Gu, Sufang.,Liu, Xiangsheng.,...&Liu, Xiangrui.(2021).Prodrug nanoparticles rationally integrating stroma modification and chemotherapy to treat metastatic pancreatic cancer.BIOMATERIALS,278.
MLA Wang, Liying,et al."Prodrug nanoparticles rationally integrating stroma modification and chemotherapy to treat metastatic pancreatic cancer".BIOMATERIALS 278(2021).

入库方式： OAI收割

来源：合肥物质科学研究院

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