Supramolecular Aggregation-Induced Emission Nanodots with Programmed Tumor Microenvironment Responsiveness for Image-Guided Orthotopic Pancreatic Cancer Therapy

被引:119
作者
Chen, Xiaohui [1 ]
Gao, Heqi [2 ,3 ]
Deng, Yongyan [1 ]
Jin, Qiao [1 ]
Ji, Jian [1 ]
Ding, Dan [2 ,3 ]
机构
[1] Zhejiang Univ, MOE Key Lab Macromol Synth & Functionalizat, Minist Educ, Dept Polymer Sci & Engn, Hangzhou 310027, Peoples R China
[2] Nankai Univ, Minist Educ, State Key Lab Med Chem Biol, Key Lab Bioact Mat, Tianjin 300071, Peoples R China
[3] Nankai Univ, Coll Life Sci, Tianjin 300071, Peoples R China
基金
国家重点研发计划; 中国国家自然科学基金;
关键词
nanotheranostics; aggregation-induced emission; pancreatic cancer; supermolecular nanomaterials; tumor microenvironment responsiveness; EPITHELIAL-MESENCHYMAL TRANSITION; DRUG-DELIVERY; GEMCITABINE; NANOPARTICLES; NANOCARRIERS; SYSTEMS; PRODRUG; CHEMOTHERAPY; COMBINATION; STRATEGY;
D O I
10.1021/acsnano.0c02197
中图分类号
O6 [化学];
学科分类号
0703 ;
摘要
Supramolecular nanomaterials as drug carriers have recently received increasing attention due to their intrinsic merits such as high stability, strong inclusion capability, and facile modification of the parental structure; however, intelligent ones with combined capacities of long blood circulation, highly efficient tumor cell uptake, and site-oriented drug release inside tumor cells are still rather limited. Herein, we report a strategy using supramolecular aggregation-induced emission (AIE) nanodots for image-guided drug delivery, which integrate both the advantages of AIE and supramolecular nanomaterials. The supramolecular AIE dots are prepared by the host-guest coassembly of the matrix metalloproteinase-2 (MMP-2) sensitive PEG-peptide (PEG(2000)-RRRRRRRR (R8)-PLGLAG-EKEKEKEKEKEK (EK6)) and functional alpha-cyclodextrins (alpha-CD) derivatives that are conjugated with the anticancer drug gemcitabine (GEM) and a far-red/near-infrared fluorescent rhodanine-3-acetic acid-based AIE luminogen, respectively. The supramolecular AIE dots realize long blood circulation time by virtue of the zwitterionic stealth peptide EK6. After largely accumulating in tumor tissues by the enhanced permeability and retention effect, the supramolecular AIE dots can successively respond to the tumor-overexpressed MMP-2 and intracellular reductive microenvironment, achieving both enhanced cancer cellular uptake and selective GEM release within cancer cells, which thus exhibit excellent tumor inhibition ability in both subcutaneous and orthotopic pancreatic tumor models.
引用
收藏
页码:5121 / 5134
页数:14
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