Journal
ACS NANO
Volume 14, Issue 4, Pages 5121-5134Publisher
AMER CHEMICAL SOC
DOI: 10.1021/acsnano.0c02197
Keywords
nanotheranostics; aggregation-induced emission; pancreatic cancer; supermolecular nanomaterials; tumor microenvironment responsiveness
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Funding
- National Natural Science Foundation of China [21774110, 51573160, 51873092, 51961160730]
- National Key R&D Program of China [2017YFE0132200]
- Fundamental Research Funds for the Central Universities, Nankai University [63191521, 63171218, 63191176]
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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.
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