Protease-Responsive Prodrug with Aggregation-Induced Emission Probe for Controlled Drug Delivery and Drug Release Tracking in Living Cells
Abstract
Controlled drug delivery and real-time tracking of drug release in cancer cells are essential for cancer therapy. Herein, we report a protease-responsive prodrug (DOX-FCPPs-PyTPE, DFP) with aggregation-induced emission (AIE) characteristics for controlled drug delivery and precise tracking of drug release in living cells. DFP consists of three components: AIE-active tetraphenylethene (TPE) derivative PyTPE, functionalized cell penetrating peptides (FCPPs) containing a cell penetrating peptide (CPP) and a short protease-responsive peptide (LGLAG) that can be selectively cleaved by a cancer-related enzyme matrix metalloproteinase-2 (MMP-2), and a therapeutic unit (doxorubicin, DOX). Without MMP-2, this prodrug cannot go inside the cells easily. In the presence of MMP-2, DFP can be cleaved into two parts. One is cell penetrating peptides (CPPs) linked DOX, which can easily interact with cell membrane and then go inside the cell with the help of CPPs. Another is the PyTPE modified peptide which will self-aggregate because of the hydrophobic interaction and turn on the yellow fluorescence of PyTPE. The appearance of the yellow fluorescence indicates the release of the therapeutic unit to the cells. The selective delivery of the drug to the MMP-2 positive cells was also confirmed by using the intrinsic red fluorescence of DOX. Our result suggests a new and promising method for controlled drug delivery and real-time tracking of drug release in MMP-2 overexpression cells.
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The frequencies of the peptides displayed on phages are not even in the library.
“Usually, the frequencies of the peptides displayed on phages are not even in the library. There were some reasons for the heterogenous phage amount, such as biases in library construction, variance in the use of cryptography,45,46 the different growth rates of phages and peptide degradation by protease.47”
From Identification of heptapeptides targeting a lethal bacterial strain in septic mice through an integrative approach (2022) · cites this paper as [47]
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Hu, J., Jiang, W., Yuan, L., Duan, C., Yuan, Q., Long, Z., Lou, X., & Xia, F. (2021) · Aggregate · doi:10.1002/agt2.10 · Cited by 172 · see citing works
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“There were some reasons for the heterogenous phage amount, such as biases in library construction, variance in the use of cryptography,(45,46) the different growth rates of phages and peptide degradation by protease.(47) To define the bias of the phage library, we analyzed the frequency distribution of heptapeptides a…”
Background
- Authors
- Cheng, Y., Huang, F., Min, X., Gao, P., Zhang, T., Li, X., Liu, B., Hong, Y., Lou, X., & Xia, F.
- Affiliations
- Huazhong University of Science and Technology (CN)
- National Engineering Research Center for Nanomedicine, Department of Biomedical Engineering, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan 430074, P. R. China
- The University of Melbourne (AU)
- Corresponding author
- Lou, Xiaoding
- Xia, Fan
- ORCID
- Venue
- Analytical Chemistry
- Publisher
- American Chemical Society (ACS)
- Published
- 2016-08-17
- Volume
- 88
- Issue
- 17
- Pages
- 8913-8919
- ISSN
- 0003-2700 (ISSN-L)
- 1520-6882
- OpenAlex
- W2511364181
- Cited by
- 94
- References
- 5
- Citations by year
- 2025: 6 · 2024: 3 · 2023: 9 · 2022: 10 · 2021: 16 · 2020: 8 · 2019: 16 · 2018: 14 · 2017: 12
- FWCI
- 6.23
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Analytical Chemistry (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Ministry of Science and Technology of the People's Republic of China (2013CB933000, 2015CB932600, 2016YFF0100800)
- University of Melbourne
- National Natural Science Foundation of China (21375042, 21405054, 21525523, 21574048)
- Special Fund for Strategic New Industry Development of Shenzhen (JCYJ20150616144425376)
- Central People's Government of the People's Republic of China
- Topics
- Physical Sciences › Materials Science › Materials Chemistry › Luminescence and Fluorescent Materials
- Physical Sciences › Materials Science › Biomaterials › Nanoparticle-Based Drug Delivery
- Physical Sciences › Chemistry › Spectroscopy › Molecular Sensors and Ion Detection
- Keywords
- aggregation-induced emission, tetraphenylethylene, cell-penetrating peptides, MMP-2, doxorubicin, controlled drug delivery, cancer cells, self-aggregation
- MeSH terms
- Antibiotics, Antineoplastic, Cell Survival, Dose-Response Relationship, Drug, Doxorubicin, Drug Screening Assays, Antitumor, Fluorescent Dyes, Humans, Prodrugs, Stilbenes, Structure-Activity Relationship, Tumor Cells, Cultured, Drug Delivery Systems, Microscopy, Confocal, Matrix Metalloproteinase 2, Cell Proliferation, Cell-Penetrating Peptides, Drug Liberation
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