Targeting cancer-associated fibroblasts by dual-responsive lipid-albumin nanoparticles to enhance drug perfusion for pancreatic tumor therapy

被引:89
作者
Yu, Qianwen
Qiu, Yue
Li, Jianping
Tang, Xian
Wang, Xuhui
Cun, Xingli
Xu, Shanshan
Liu, Yayuan
Li, Man
Zhang, Zhirong
He, Qin [1 ]
机构
[1] Sichuan Univ, West China Sch Pharm, Key Lab Drug Targeting & Drug Delivery Syst, Sichuan Engn Lab Plant Sourced Drug,Educ Minist, Chengdu 610064, Peoples R China
基金
中国国家自然科学基金;
关键词
Pancreatic tumor; Thermosensitive liposomes; Cancer-associated fibroblasts; Deep penetration; Chemo-photothermal therapy; PARTICLE-SIZE; EFFICACY; DELIVERY; ACCUMULATION; PENETRATION; EXOCYTOSIS; LIPOSOMES; PROMOTES; CARRIER; SHAPE;
D O I
10.1016/j.jconrel.2020.02.040
中图分类号
O6 [化学];
学科分类号
0703 ;
摘要
Pancreatic ductal adenocarcinoma (PDAC) is rich in cancer-associated fibroblasts (CAFs), which participate in the formation of tumor stroma. However, the dense tumor stroma of PDAC presents major barriers to drug delivery, resulting in an obstacle for PDAC therapy. Considering the special tumor microenvironment of PDAC, we constructed a novel nanoparticle which is responsive to the membrane biomarker FAP-alpha on CAFs and nearinfrared (NIR) laser irradiation. Small sized albumin nanoparticle of paclitaxel (HSA-PTX) with strong tumorpenetration ability was encapsulated into the CAP-(a FAP-alpha responsive cleavable amphiphilic peptide) modified thermosensitive liposomes (CAP-TSL). Moreover, IR-780, a photothermal agent, was incorporated into CAP-TSL to afford CAP-ITSL. The designed HSA-PTX@CAP-ITSL increased the drug retention of HSA-PTX in solid tumor and HSA-PTX was released via FAP-alpha (specifically expresses on CAFs) triggered. Under sequential stimulation of NIR laser irradiation, IR-780 produced hyperthermia to kill tumor cells and expand the tumor interstitial space at the same time, which further promoted the release of small sized HSA-PTX in deep tumor regions. Consequently, the excellent antitumor efficacy of HSA-PTX@CAP-ITSL was demonstrated in Pan 02 subcutaneous and orthotopic tumor mouse models. Therefore, HSA-PTX@CAP-ITSL well combined chemotherapy with photothermal therapy, providing a promising drug delivery strategy for PDAC treatment.
引用
收藏
页码:564 / 575
页数:12
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