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

doi:10.1016/j.biomaterials.2021.121176

	Prodrug nanoparticles rationally integrating stroma modification and chemotherapy to treat metastatic pancreatic cancer
	Wang, Liying 1,2,3,10,11; Liu, Zimo 2,3,10,11; Zhou, Quan 2,3; Gu, Sufang 2,3; Liu, Xiangsheng 4; Huang, Jianxiang 2,3; Jiang, Haiping 5; Wang, Huifang 2,3; Cao, Liping 9; Sun, Jihong 1
刊名	BIOMATERIALS
	2021-11-01
卷号	278
关键词	Pancreatic cancer Polymeric prodrug Calcipotriol Cancer-associated fibroblast Metastasis
ISSN号	0142-9612
DOI	10.1016/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
出版者	ELSEVIER SCI LTD
WOS记录号	WOS:000710782400001
内容类型	期刊论文
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, Canc Ctr, Hangzhou 310058, Peoples R China 7.Natl Ctr Nanosci & Technol, CAS Ctr Excellence Nanosci, Beijing 100190, Peoples R China 8.Natl Ctr Nanosci & Technol, CAS Key Lab Biomed Effects Nanomat & Nanosafety, Beijing 100190, Peoples R China 9.Zhejiang Univ, Sir Run Run Shaw Hosp, Dept Gen Surg, Sch Med, Hangzhou 310016, 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).