ROS-Activated Ratiometric Fluorescent Polymeric Nanoparticles for Self-Reporting Drug Delivery
Abstract
Reactive oxygen species (ROS)-responsive theranostic nanomedicines have attracted wide interest in recent years because ROS stress is implicated in some pathological disorders such as inflammatory diseases and cancers. In this article, we report a kind of innovative ROS-responsive theranostic polymeric nanoparticles that are able to load hydrophobic drugs and to fluorescently self-report the in vitro or intracellular drug release under ROS triggering. The fluorescent nanoparticles were formed by amphiphilic block copolymers consisting of a poly(ethylene glycol) (PEG) segment and an oxidation-responsive hydrophobic block. The copolymers with different hydrophobic block lengths were synthesized by the atom transfer radical polymerization of a phenylboronic ester-containing acrylic monomer with a small fraction of a ROS-activatable 1,8-naphthalimide-based fluorescent monomer, using PEG–Br as the macroinitiator. The copolymer nanoparticles were stable in neutral phosphate buffer but degraded upon H 2 O 2 triggering, with the degradation rate depending on the hydrophobic block length and the concentration of H 2 O 2 . The degradation of nanoparticles was accompanied by a colorimetric change of the fluorophore from blue to green, which affords the nanoparticles the ability to detecting H 2 O 2 by a ratiometric fluorescent approach. Moreover, the nanoparticles could encapsulate doxorubicin (DOX) and the H 2 O 2 -triggered DOX release was well associated with the change in ratiometric fluorescence. Confocal laser scanning microscope results reveal that the fluorescent nanoparticles were internalized into A549 cells through the endocytosis pathway. The ROS-stimulated degradation of the nanoparticles and intracellular DOX release and the fate of the degraded polymers could be monitored by ratiometric fluorescent imaging. Finally, the naked nanoparticles and the degradation products are cytocompatible, whereas the DOX-loaded ones exhibit concentration-dependent cytotoxicity. Of importance, the stimulation with exogenous H 2 O 2 or lipopolysaccharide enhanced obviously the cell-killing capability of the DOX-loaded nanoparticles because of the ROS-enhanced intracellular DOX release.
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Exogenous H2O2 and lipopolysaccharide-assisted stimulation enabled the remarkable diminishing of cancer cells.
“Moreover, exogenous H2O2 and lipopolysaccharide-assisted stimulation enabled the remarkable diminishing of cancer cells.”
From Recent Advances in Nanomicelles Delivery Systems. (2020) · cites this paper as [218]
DOX was encapsulated in these nanomicelles, where its release was induced by H2O2 and monitored via the change in the ratiometric fluorescence.
“Afterwards, DOX was encapsulated in these nanomicelles, where its release was induced by H2O2 and monitored via the change in the ratiometric fluorescence.”
From Recent Advances in Nanomicelles Delivery Systems. (2020) · cites this paper as [218]
DOX-loaded nanoparticles showed concentration-dependent cytotoxicity, whereas naked ones and their degradation residues were cytocompatible.
“As a result, DOX-loaded nanoparticles showed concentration-dependent cytotoxicity, whereas naked ones and their degradation residues were cytocompatible.”
From Recent Advances in Nanomicelles Delivery Systems. (2020) · cites this paper as [218]
Li's group reported the design of amphiphilic block copolymer containing PEG which is prone to form nanomicelles.
“Recently, Li’s group reported the design of amphiphilic block copolymer containing PEG which is prone to form nanomicelles [218].”
From Recent Advances in Nanomicelles Delivery Systems. (2020) · cites this paper as [218]
Confocal laser scanning microscopy showed endocytosis of such fluorescent nanoparticles into A549 cells.
“Confocal laser scanning microscopy showed endocytosis of such fluorescent nanoparticles into A549 cells.”
From Recent Advances in Nanomicelles Delivery Systems. (2020) · cites this paper as [218]
Cites
ROS function in redox signaling and oxidative stress
Schieber, M., & Chandel, N. S. (2014) · Current Biology · doi:10.1016/j.cub.2014.03.034 · Cited by 6,931 · see citing works
A role for mitochondria in nlrp3 inflammasome activation
Zhou, R., Yazdi, A. S., Menu, P., & Tschopp, J. (2011) · Nature · doi:10.1038/nature09663 · Cited by 5,602 · see citing works
Modulation of oxidative stress as an anticancer strategy
Gorrini, C., Harris, I. S., & Mak, T. W. (2013) · Nature Reviews Drug Discovery · doi:10.1038/nrd4002 · Cited by 3,579 · see citing works
Reconciling the chemistry and biology of reactive oxygen species
Winterbourn, C. C. (2008) · Nature Chemical Biology · doi:10.1038/nchembio.85 · Cited by 2,504 · see citing works
The role of iron and reactive oxygen species in cell death
Dixon, S. J., & Stockwell, B. R. (2014) · Nature Chemical Biology · doi:10.1038/nchembio.1416 · Cited by 2,381 · see citing works
ROS stress in cancer cells and therapeutic implications.
Pelicano, H., Carney, D., & Huang, P. (2004) · Drug resistance updates · doi:10.1016/j.drup.2004.01.004 · Cited by 1,992 · see citing works
Reaction-based small-molecule fluorescent probes for chemoselective bioimaging
Chan, J., Dodani, S. C., & Chang, C. J. (2012) · Nature Chemistry · doi:10.1038/nchem.1500 · Cited by 1,890 · see citing works
A tissue-scale gradient of hydrogen peroxide mediates rapid wound detection in zebrafish
Niethammer, P., Grabher, C., Look, A. T., & Mitchison, T. J. (2009) · Nature · doi:10.1038/nature08119 · Cited by 1,541 · see citing works
Nanochemistry and Nanomedicine for Nanoparticle-based Diagnostics and Therapy
Chen, G., Roy, I., Yang, C., & Prasad, P. N. (2016) · Chemical Reviews · doi:10.1021/acs.chemrev.5b00148 · Cited by 1,507 · see citing works
Imaging and drug delivery using theranostic nanoparticles
Janib, S. M., Moses, A. S., & MacKay, J. A. (2010) · Advanced Drug Delivery Reviews · doi:10.1016/j.addr.2010.08.004 · Cited by 1,249 · see citing works
Chen, X., Wang, F., Hyun, J. Y., Wei, T., Qiang, J., Ren, X., Shin, I., & Yoon, J. (2016) · Chemical Society Reviews · doi:10.1039/c6cs00192k · Cited by 1,169 · see citing works
Rethinking cancer nanotheranostics
Chen, H., Zhang, W., Zhu, G., Xie, J., & Chen, X. S. (2017) · Nature Reviews Materials · doi:10.1038/natrevmats.2017.24 · Cited by 1,107 · see citing works
Rational Design of Cancer Nanomedicine: Nanoproperty Integration and Synchronization
Sun, Q., Zhou, Z., Qiu, N., & Shen, Y. (2017) · Advanced Materials · doi:10.1002/adma.201606628 · Cited by 1,063 · see citing works
Wang, Y., Zhou, K., Huang, G., Hensley, C. T., Huang, X., Ma, X., Zhao, T., Sumer, B. D., DeBerardinis, R. J., & Gao, J. (2013) · Nature Materials · doi:10.1038/nmat3819 · Cited by 776 · see citing works
Gupta, S. C., Hevia, D., Patchva, S., Park, B., Koh, W., & Aggarwal, B. B. (2011) · Antioxidants and Redox Signaling · doi:10.1089/ars.2011.4414 · Cited by 736 · see citing works
Muthu, M. S., Leong, D. T., Mei, L., & Feng, S. (2014) · Theranostics · doi:10.7150/thno.8698 · Cited by 609 · see citing works
Role of Reactive Oxygen Species (ROS) in Therapeutics and Drug Resistance in Cancer and Bacteria
Allimuthu, D. (2017) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.6b01243 · Cited by 583 · see citing works
Srikun, D., Miller, E. W., Domaille, D. W., et al. (2008) · Journal of the American Chemical Society · doi:10.1021/ja711480f · Cited by 544 · see citing works
Polymeric Nanostructures for Imaging and Therapy
Elsabahy, M., Heo, G. S., Lim, S., Sun, G., & Wooley, K. L. (2015) · Chemical Reviews · doi:10.1021/acs.chemrev.5b00135 · Cited by 507 · see citing works
ROS‐Responsive Polyprodrug Nanoparticles for Triggered Drug Delivery and Effective Cancer Therapy
Xu, X., Saw, P. E., Tao, W., Li, Y., Ji, X., Bhasin, S., Liu, Y., Ayyash, D., Rasmussen, J., Huo, M., et al. (2017) · Advanced Materials · doi:10.1002/adma.201700141 · Cited by 501 · see citing works
Kievit, F. M., & Zhang, M. (2011) · Advanced Materials · doi:10.1002/adma.201102313 · Cited by 495 · see citing works
Self-citationNoninvasive Imaging of Nanomedicines and Nanotheranostics: Principles, Progress, and Prospects
Kunjachan, S., Ehling, J., Storm, G., Kiessling, F. M., & Lammers, T. (2015) · Chemical Reviews · doi:10.1021/cr500314d · Cited by 480 · see citing works
Noh, J., Kwon, B., Han, E., Park, M., Yang, W., Cho, W., Yoo, W., Khang, G., & Lee, D. (2015) · Nature Communications · doi:10.1038/ncomms7907 · Cited by 462 · see citing works
de Bittner, G. C. V., Goun, E. A., Bertozzi, C. R., & Chang, C. J. (2010) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1012864107 · Cited by 403 · see citing works
Tumor Redox Heterogeneity‐Responsive Prodrug Nanocapsules for Cancer Chemotherapy
Wang, J., Sun, X., Mao, W., Sun, W., Tang, J., Sui, M., Shen, Y., & Gu, Z. (2013) · Advanced Materials · doi:10.1002/adma.201300929 · Cited by 394 · see citing works
Reactive Oxygen Species (ROS) Responsive Polymers for Biomedical Applications
Xu, Q., He, C., Xiao, C., & Chen, X. (2016) · Macromolecular Bioscience · doi:10.1002/mabi.201500440 · Cited by 365 · see citing works
Current Progress in Reactive Oxygen Species (ROS)‐Responsive Materials for Biomedical Applications
Lee, S. H., Gupta, M. K., Bang, J. B., Bae, H., & Sung, H. (2013) · Advanced Healthcare Materials · doi:10.1002/adhm.201200423 · Cited by 350 · see citing works
Hydrogen Peroxide Inducible DNA Cross-Linking Agents: Targeted Anticancer Prodrugs
Kuang, Y., Balakrishnan, K., Gandhi, V. V., & Peng, X. (2011) · Journal of the American Chemical Society · doi:10.1021/ja2073824 · Cited by 311 · see citing works
Yuan, Y., Liu, J., & Liu, B. (2014) · Angewandte Chemie International Edition · doi:10.1002/anie.201402189 · Cited by 303 · see citing works
Cell-Specific, Activatable, and Theranostic Prodrug for Dual-Targeted Cancer Imaging and Therapy
Santra, S., Kaittanis, C., Santiesteban, O. J., & Perez, J. M. (2011) · Journal of the American Chemical Society · doi:10.1021/ja207463b · Cited by 296 · see citing works
An Activatable Prodrug for the Treatment of Metastatic Tumors
Kim, E. J., Bhuniya, S., Lee, H., Kim, H. M., Cheong, C., Maiti, S., Hong, K. S., & Kim, J. S. (2014) · Journal of the American Chemical Society · doi:10.1021/ja5077684 · Cited by 269 · see citing works
Tapeinos, C., & Pandit, A. S. (2016) · Advanced Materials · doi:10.1002/adma.201505376 · Cited by 237 · see citing works
Hydrogen peroxide fuels aging, inflammation, cancer metabolism and metastasis
Lisanti, M. P., Martinez‐Outschoorn, U., Zhao, L., Pavlides, S., Whitaker‐Menezes, D., Pestell, R. G., Howell, A., & Sotgia, F. (2011) · Cell Cycle · doi:10.4161/cc.10.15.16870 · Cited by 234 · see citing works
Wang, H., Di, J., Sun, Y., Fu, J., Wei, Z., Matsui, H., Alonso, A. D. C., & Zhou, S. (2015) · Advanced Functional Materials · doi:10.1002/adfm.201501524 · Cited by 232 · see citing works
Targeted Nanotheranostics for Future Personalized Medicine: Recent Progress in Cancer Therapy
Jo, S. D., Ku, S. H., Won, Y.-Y., Kim, S. H., & Kwon, I. C. (2016) · Theranostics · doi:10.7150/thno.15335 · Cited by 218 · see citing works
Li, Y., Hu, K., Yu, Y., Rotenberg, S. A., Amatore, C. A., & Mirkin, M. V. (2017) · Journal of the American Chemical Society · doi:10.1021/jacs.7b06476 · Cited by 216 · see citing works
Kumar, R., Han, J., Lim, H., Ren, W. X., Lim, J.-Y., Kim, J., & Kim, J. S. (2014) · Journal of the American Chemical Society · doi:10.1021/ja510421q · Cited by 213 · see citing works
A transistor-like pH nanoprobe for tumour detection and image-guided surgery
Zhao, T., Huang, G., Li, Y., Yang, S.-C., Ramezani, S. M., Lin, Z., Wang, Y., Ma, X., Zeng, Z., Luo, M., et al. (2016) · Nature Biomedical Engineering · doi:10.1038/s41551-016-0006 · Cited by 207 · see citing works
Yuan, Y., Zhang, C., Xu, S., & Liu, B. (2015) · Chemical Science · doi:10.1039/c5sc03583j · Cited by 205 · see citing works
Oxidation-responsive polymers for biomedical applications
Song, C., Du, F., & Li, Z. (2014) · Journal of Materials Chemistry B · doi:10.1039/c3tb21725f · Cited by 202 · see citing works
Self-citationSong, Z., Mao, D., Sung, S. H. P., Kwok, R. T. K., Lam, J. W. Y., Kong, D., Ding, D., & Tang, B. Z. (2016) · Advanced Materials · doi:10.1002/adma.201601214 · Cited by 201 · see citing works
Pu, H.-L., Chiang, W., Maiti, B., Liao, Z., Ho, Y., Shim, M. S., Chuang, E., Younan Xia, A., & Sung, H. (2014) · ACS Nano · doi:10.1021/nn4058787 · Cited by 197 · see citing works
Exhaled breath analysis: Novel approach for early detection of lung cancer
Chan, H. P., Lewis, C. R., & Thomas, P. S. (2008) · Lung Cancer · doi:10.1016/j.lungcan.2008.05.020 · Cited by 183 · see citing works
Liu, L., Qiu, W., Li, B., Zhang, C., Sun, L., Wan, S., Rong, L., & Zhang, X. (2016) · Advanced Functional Materials · doi:10.1002/adfm.201602541 · Cited by 178 · see citing works
Inflammation-Responsive Antioxidant Nanoparticles Based on a Polymeric Prodrug of Vanillin
Kwon, J., Kim, J.-H., Park, S., Khang, G., Kang, P. M., & Lee, D. (2013) · Biomacromolecules · doi:10.1021/bm400256h · Cited by 157 · see citing works
Polymeric assemblies and nanoparticles with stimuli-responsive fluorescence emission characteristics
Li, C., & Liu, S. (2012) · Chemical Communications · doi:10.1039/c2cc17695e · Cited by 150 · see citing works
Fluorescence optical imaging in anticancer drug delivery
Etrych, T., Lucas, H., Janoušková, O., Chytil, P., Mueller, T., & Mäder, K. (2016) · Journal of Controlled Release · doi:10.1016/j.jconrel.2016.02.022 · Cited by 137 · see citing works
Hydrogen Peroxide Activated Matrix Metalloproteinase Inhibitors: A Prodrug Approach
Jourden, J. L. M., & Cohen, S. M. (2010) · Angewandte Chemie International Edition · doi:10.1002/anie.201003819 · Cited by 127 · see citing works
Hu, X., Li, Y., Liu, T., et al. (2015) · ACS Applied Materials & Interfaces · doi:10.1021/acsami.5b04025 · Cited by 121 · see citing works
Huang, X., Du, F., Cheng, J., Dong, Y., Liang, D., Ji, S., Lin, S., & Li, Z. (2009) · Macromolecules · doi:10.1021/ma802138r · Cited by 114 · see citing works
Self-citationOxidation-Accelerated Hydrolysis of the Ortho Ester-Containing Acid-Labile Polymers
Song, C., Ji, R., Du, F., et al. (2013) · ACS Macro Letters · doi:10.1021/mz4000392 · Cited by 113 · see citing works
Self-citationSu, Z., Chen, M., Xiao, Y., Sun, M., Zong, L., Asghar, S., Dong, M., Li, H., Ping, Q. N., & Zhang, C. (2014) · Journal of Controlled Release · doi:10.1016/j.jconrel.2014.09.020 · Cited by 111 · see citing works
Activatable fluorescence: From small molecule to nanoparticle
Luby, B. M., Charron, D. M., MacLaughlin, C. M., & Zheng, G. (2016) · Advanced Drug Delivery Reviews · doi:10.1016/j.addr.2016.08.010 · Cited by 103 · see citing works
Yan, J., Ji, W., Chen, E., et al. (2008) · Macromolecules · doi:10.1021/ma7026726 · Cited by 98 · see citing works
Intelligent nucleic acid delivery systems based on stimuli-responsive polymers
Du, F., Wang, Y., Zhang, R., & Li, Z. (2009) · Soft Matter · doi:10.1039/b915020j · Cited by 91 · see citing works
Self-citationChen, K., Chiu, Y., Chen, Y., et al. (2011) · Biomaterials · doi:10.1016/j.biomaterials.2010.11.069 · Cited by 79 · see citing works
Yin, W., Li, J., Ke, W., Zha, Z., & Ge, Z. (2017) · ACS Applied Materials & Interfaces · doi:10.1021/acsami.7b08347 · Cited by 79 · see citing works
Lin, W., Li, Y., Zhang, W., et al. (2016) · ACS Applied Materials & Interfaces · doi:10.1021/acsami.6b07103 · Cited by 65 · see citing works
Hydrogen peroxide-responsive anticancer hyperbranched polymer micelles for enhanced cell apoptosis
Liu, B., Wang, D., Liu, Y., Zhang, Q., Meng, L., Chi, H., Shi, J., Li, G., Li, J., & Zhu, X. (2015) · Polymer Chemistry · doi:10.1039/c5py00257e · Cited by 63 · see citing works
Rapid, Simple, and High‐Throughput Antimicrobial Susceptibility Testing and Antibiotics Screening
Zhu, C., Yang, Q., Liu, L., et al. (2011) · Angewandte Chemie International Edition · doi:10.1002/anie.201103381 · Cited by 60 · see citing works
Deng, Z., Hu, J., & Liu, S. (2017) · Macromolecular Rapid Communications · doi:10.1002/marc.201600685 · Cited by 56 · see citing works
Li, M., Li, S., Chen, H., et al. (2015) · ACS Applied Materials & Interfaces · doi:10.1021/acsami.5b11846 · Cited by 55 · see citing works
Qiao, Z., Zhao, W., Cong, Y., et al. (2016) · Biomacromolecules · doi:10.1021/acs.biomac.6b00041 · Cited by 55 · see citing works
Krüger, H. R., Schütz, I., Justies, A., Licha, K., Welker, P., Haucke, V., & Calderón, M. (2014) · Journal of Controlled Release · doi:10.1016/j.jconrel.2014.08.018 · Cited by 47 · see citing works
Chu, T., Lü, R., & Liu, B. (2016) · Biosensors and Bioelectronics · doi:10.1016/j.bios.2016.07.039 · Cited by 43 · see citing works
d’Arcy, R., & Tirelli, N. (2014) · Polymers for Advanced Technologies · doi:10.1002/pat.3264 · Cited by 37 · see citing works
Bioimaging with Macromolecular Probes Incorporating Multiple BODIPY Fluorophores
Thapaliya, E. R., Zhang, Y., Dhakal, P., et al. (2017) · Bioconjugate Chemistry · doi:10.1021/acs.bioconjchem.7b00166 · Cited by 34 · see citing works
Viger, M. L., Collet, G., Lux, J., Huu, V. A. N., Gumá, M., Foucault‐Collet, A., Olejniczak, J., Joshi-Barr, S., Firestein, G. S., & Almutairi, A. (2017) · Biomaterials · doi:10.1016/j.biomaterials.2017.03.042 · Cited by 33 · see citing works
Dual-Modal Tumor Imaging via Long-Circulating Biodegradable Core-Cross-Linked Polymeric Micelles
Zhao, J., Song, S., Zhong, M., & Li, C. (2011) · ACS Macro Letters · doi:10.1021/mz200034f · Cited by 27 · see citing works
Stimuli‐Responsive Electrodes Detect Oxidative Stress and Liver Injury
Aran, K., Paredes, J., Rafi, M., Yau, J. F., Acharya, A. P., Zibinsky, M., Liepmann, D., & Murthy, N. (2014) · Advanced Materials · doi:10.1002/adma.201404562 · Cited by 19 · see citing works
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Recent Advances in Nanomicelles Delivery Systems.
Tawfik, S. M., Azizov, S., Elmasry, M. R., Sharipov, M., & Lee, Y.-I. (2020) · Nanomaterials · doi:10.3390/nano11010070 · Cited by 156 · see citing works
“Recently, Li’s group reported the design of amphiphilic block copolymer containing PEG which is prone to form nanomicelles [218].”
Background
- Authors
- Zhang, M., Song, C.-C., Su, S., Du, F.-S., & Li, Z.-C.
- Affiliations
- Peking University (CN)
- Beijing National Laboratory for Molecular Sciences (BNLMS), Key Laboratory of Polymer Chemistry & Physics of Ministry of Education, Department of Polymer Science & Engineering, College of Chemistry and Molecular Engineering, Peking University, Beijing 100871, China
- Corresponding author
- Du, Fu-Sheng
- Venue
- ACS Applied Materials & Interfaces
- Publisher
- American Chemical Society (ACS)
- Published
- 2018-02-09
- Volume
- 10
- Issue
- 9
- Pages
- 7798-7810
- ISSN
- 1944-8244 (ISSN-L)
- 1944-8252
- OpenAlex
- W2789077574
- Cited by
- 64
- References
- 70
- Citations by year
- 2026: 6 · 2025: 6 · 2024: 4 · 2023: 6 · 2022: 6 · 2021: 11 · 2020: 10 · 2019: 13 · 2018: 2
- FWCI
- 2.91
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- ACS Applied Materials & Interfaces (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Ministry of Science and Technology of the People's Republic of China (2016YFA0201400)
- National Natural Science Foundation of China (21534001, 21474001)
- Topics
- Physical Sciences › Materials Science › Biomaterials › Nanoparticle-Based Drug Delivery
- Physical Sciences › Engineering › Biomedical Engineering › Nanoplatforms for cancer theranostics
- Physical Sciences › Materials Science › Materials Chemistry › Luminescence and Fluorescent Materials
- Keywords
- reactive oxygen species-responsive nanoparticles, ratiometric fluorescence, nanotheranostics, atom transfer radical polymerization, doxorubicin release, intracellular drug release, endocytosis, lipopolysaccharide, cytotoxicity
- MeSH terms
- Doxorubicin, Drug Carriers, Hydrogen Peroxide, Micelles, Polyethylene Glycols, Drug Delivery Systems, Reactive Oxygen Species, Nanoparticles
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