Good Steel Used in the Blade: Well‐Tailored Type‐I Photosensitizers with Aggregation‐Induced Emission Characteristics for Precise Nuclear Targeting Photodynamic Therapy
Open accessAbstract
Photodynamic therapy (PDT) has long been recognized to be a promising approach for cancer treatment. However, the high oxygen dependency of conventional PDT dramatically impairs its overall therapeutic efficacy, especially in hypoxic solid tumors. Exploration of distinctive PDT strategy involving both high‐performance less‐oxygen‐dependent photosensitizers (PSs) and prominent drug delivery system is an appealing yet significantly challenging task. Herein, a precise nuclear targeting PDT protocol based on type‐I PSs with aggregation‐induced emission (AIE) characteristics is fabricated for the first time. Of the two synthesized AIE PSs, TTFMN is demonstrated to exhibit superior AIE property and stronger type‐I reactive oxygen species (ROS) generation efficiency owing to the introduction of tetraphenylethylene and smaller singlet–triplet energy gap, respectively. With the aid of a lysosomal acid‐activated TAT‐peptide‐modified amphiphilic polymer poly(lactic acid)12k–poly(ethylene glycol)5k–succinic anhydride‐modified TAT, the corresponding TTFMN‐loaded nanoparticles accompanied with acid‐triggered nuclear targeting peculiarity can quickly accumulate in the tumor site, effectively generate type‐I ROS in the nuclear region and significantly suppress the tumor growth under white light irradiation with minimized systematic toxicity. This delicate “Good Steel Used in the Blade” tactic significantly maximizes the PDT efficacy and offers a conceptual while practical paradigm for optimized cancer treatment in further translational medicine.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
Siegel, R. L., Miller, K. D., & Jemal, A. (2019) · CA: A Cancer Journal for Clinicians · doi:10.3322/caac.21551 · Cited by 20,160 · see citing works
The ORCA quantum chemistry program package
Neese, F., Wennmohs, F., Becker, U., & Riplinger, C. (2020) · The Journal of Chemical Physics · doi:10.1063/5.0004608 · Cited by 5,268 · see citing works
Photodynamic therapy of cancer: An update
Agostinis, P., Berg, K., Cengel, K. A., Foster, T. H., Girotti, A. W., Gollnick, S. O., Hahn, S. M., Hamblin, M. R., Juzeniene, A., Kessel, D., et al. (2011) · CA: A Cancer Journal for Clinicians · doi:10.3322/caac.20114 · Cited by 5,145 · see citing works
Generation and Detection of Reactive Oxygen Species in Photocatalysis
Nosaka, Y., & Nosaka, A. Y. (2017) · Chemical Reviews · doi:10.1021/acs.chemrev.7b00161 · Cited by 4,816 · see citing works
Photodynamic therapy and anti-tumour immunity
Castaño, A. P., Mróz, P., & Hamblin, M. R. (2006) · Nature reviews. Cancer · doi:10.1038/nrc1894 · Cited by 2,685 · see citing works
HOW DOES PHOTODYNAMIC THERAPY WORK?
Henderson, B. W., & Dougherty, T. J. (1992) · Photochemistry and Photobiology · doi:10.1111/j.1751-1097.1992.tb04222.x · Cited by 2,376 · see citing works
Reactive oxygen species generating systems meeting challenges of photodynamic cancer therapy
Zhou, Z., Song, J., Nie, L., & Chen, X. S. (2016) · Chemical Society Reviews · doi:10.1039/c6cs00271d · Cited by 2,104 · see citing works
Photosensitizers of the porphyrin and phthalocyanine series for photodynamic therapy
Bonnett, R. (1995) · Chemical Society Reviews · doi:10.1039/cs9952400019 · Cited by 2,044 · see citing works
Chemodynamic Therapy: Tumour Microenvironment‐Mediated Fenton and Fenton‐like Reactions
Tang, Z., Liu, Y., He, M., & Bu, W. (2018) · Angewandte Chemie International Edition · doi:10.1002/anie.201805664 · Cited by 1,958 · see citing works
Fluorescence probes used for detection of reactive oxygen species
Gomes, A., Fernandes, E., & Lima, J. L. F. C. (2005) · Journal of Biochemical and Biophysical Methods · doi:10.1016/j.jbbm.2005.10.003 · Cited by 1,844 · see citing works
Overcoming the Achilles' heel of photodynamic therapy
Fan, W., Huang, P., & Chen, X. S. (2016) · Chemical Society Reviews · doi:10.1039/c6cs00616g · Cited by 1,686 · see citing works
Aggregation‐Induced Emission: New Vistas at the Aggregate Level
Zhao, Z., Zhang, H., Lam, J. W. Y., & Tang, B. Z. (2020) · Angewandte Chemie International Edition · doi:10.1002/anie.201916729 · Cited by 1,441 · see citing works
Self-citationSinglet oxygen: there is indeed something new under the sun
Ogilby, P. R. (2010) · Chemical Society Reviews · doi:10.1039/b926014p · Cited by 1,270 · see citing works
Classical Nuclear Localization Signals: Definition, Function, and Interaction with Importin α
Lange, A., Mills, R. E., Lange, C. J., Stewart, M., Devine, S. E., & Corbett, A. H. (2006) · Journal of Biological Chemistry · doi:10.1074/jbc.r600026200 · Cited by 1,168 · see citing works
Cell-Penetrating Peptides: From Basic Research to Clinics
Guidotti, G., Brambilla, L., & Rossi, D. (2017) · Trends in Pharmacological Sciences · doi:10.1016/j.tips.2017.01.003 · Cited by 1,158 · see citing works
Weller, A. (1982) · Zeitschrift für Physikalische Chemie · doi:10.1524/zpch.1982.133.1.093 · Cited by 1,107 · see citing works
Pan, L., He, Q., Liu, J., Chen, Y., Ma, M., Zhang, L., & Shi, J. (2012) · Journal of the American Chemical Society · doi:10.1021/ja211035w · Cited by 985 · see citing works
Type I and Type II Photosensitized Oxidation Reactions: Guidelines and Mechanistic Pathways
Baptista, M. S., Cadet, J., Mascio, P. D., Ghogare, A. A., Greer, A., Hamblin, M. R., Lorente, C., Núñez, S. C., Ribeiro, M. S., Thomas, A. H., et al. (2017) · Photochemistry and Photobiology · doi:10.1111/php.12716 · Cited by 924 · see citing works
Photophysics and photochemistry of photodynamic therapy: fundamental aspects
Plaetzer, K., Krammer, B. E., Berlanda, J., Berr, F., & Kiesslich, T. (2008) · Lasers in Medical Science · doi:10.1007/s10103-008-0539-1 · Cited by 894 · see citing works
Chemical Design and Synthesis of Functionalized Probes for Imaging and Treating Tumor Hypoxia
Liu, J., Bu, W., & Shi, J. (2017) · Chemical Reviews · doi:10.1021/acs.chemrev.6b00525 · Cited by 840 · see citing works
Emerging Strategies of Cancer Therapy Based on Ferroptosis
Shen, Z., Song, J., Yung, B. C., Zhou, Z., Wu, A., & Chen, X. S. (2018) · Advanced Materials · doi:10.1002/adma.201704007 · Cited by 740 · see citing works
Li, M., Xia, J., Tian, R., Wang, J., Fan, J., Du, J., Long, S., Song, X., Foley, J. W., & Peng, X. (2018) · Journal of the American Chemical Society · doi:10.1021/jacs.8b08658 · Cited by 676 · see citing works
Aggregation‐enhanced theranostics: AIE sparkles in biomedical field
Kang, M., Zhang, Z., Song, N., Li, M., Sun, P., Chen, X., Wang, D., & Tang, B. Z. (2020) · Aggregate · doi:10.1002/agt2.7 · Cited by 485 · see citing works
Self-citationNguyen, V.-N., Qi, S., Kim, S., Kwon, N., Kim, G., Yim, Y., Park, S., & Yoon, J. (2019) · Journal of the American Chemical Society · doi:10.1021/jacs.9b09220 · Cited by 457 · see citing works
Zhang, Z., Xu, W., Kang, M., Wen, H., Guo, H., Zhang, P., Xi, L., Li, K., Wang, L., Wang, D., et al. (2020) · Advanced Materials · doi:10.1002/adma.202003210 · Cited by 436 · see citing works
Self-citationLi, X., Lee, D., Huang, J., & Yoon, J. (2018) · Angewandte Chemie International Edition · doi:10.1002/anie.201806551 · Cited by 426 · see citing works
Kang, M., Zhou, C., Wu, S., Yu, B., Zhang, Z., Song, N., Lee, M. M. S., Xu, W., Xu, F., Wang, D., et al. (2019) · Journal of the American Chemical Society · doi:10.1021/jacs.9b07162 · Cited by 417 · see citing works
Self-citationTumor hypoxia: its impact on cancer therapy
Moulder, J. E., & Rockwell, S. (1987) · Cancer and Metastasis Reviews · doi:10.1007/bf00055376 · Cited by 413 · see citing works
Semiconducting Polymer Nanomaterials as Near-Infrared Photoactivatable Protherapeutics for Cancer
Li, J., & Pu, K. (2020) · Accounts of Chemical Research · doi:10.1021/acs.accounts.9b00569 · Cited by 412 · see citing works
Unimolecular Photodynamic O 2 -Economizer To Overcome Hypoxia Resistance in Phototherapeutics
Li, M., Shao, Y., Kim, J. H., Pu, Z., Zhao, X., Huang, H., Xiong, T., Kang, Y., Li, G., Shao, K., et al. (2020) · Journal of the American Chemical Society · doi:10.1021/jacs.0c00734 · Cited by 398 · see citing works
Targeted Charge‐Reversal Nanoparticles for Nuclear Drug Delivery
Xu, P., Kirk, E. A. V., Zhan, Y., Murdoch, W. J., Radosz, M., & Shen, Y. (2007) · Angewandte Chemie International Edition · doi:10.1002/anie.200605254 · Cited by 371 · see citing works
Wan, Q., Zhang, R., Zhuang, Z., Li, Y., Huang, Y., Wang, Z., Zhang, W., Hou, J., & Tang, B. Z. (2020) · Advanced Functional Materials · doi:10.1002/adfm.202002057 · Cited by 365 · see citing works
Self-citationLi, M., Xiong, T., Du, J., Tian, R., Xiao, M. W., Guo, L., Long, S., Fan, J., Sun, W. C., Shao, K., et al. (2019) · Journal of the American Chemical Society · doi:10.1021/jacs.8b13141 · Cited by 345 · see citing works
Acid-Active Cell-Penetrating Peptides for in Vivo Tumor-Targeted Drug Delivery
Jin, E., Zhang, B., Sun, X., Zhou, Z., Ma, X., Sun, Q., Tang, J., Shen, Y., Kirk, E. V., Murdoch, W. J., et al. (2012) · Journal of the American Chemical Society · doi:10.1021/ja311180x · Cited by 330 · see citing works
Titanium-Based Nanoscale Metal–Organic Framework for Type I Photodynamic Therapy
Lan, G., Ni, K., Veroneau, S. S., Feng, X., Nash, G. T., Luo, T., Xu, Z., & Lin, W. (2019) · Journal of the American Chemical Society · doi:10.1021/jacs.8b13804 · Cited by 319 · see citing works
Zhuang, Z., Dai, J., Yu, M., Li, J., Shen, P., Hu, R., Lou, X., Zhao, Z., & Tang, B. Z. (2020) · Chemical Science · doi:10.1039/d0sc00785d · Cited by 291 · see citing works
Self-citationCancer cell nucleus-targeting nanocomposites for advanced tumor therapeutics
Pan, L., Liu, J., & Shi, J. (2018) · Chemical Society Reviews · doi:10.1039/c8cs00081f · Cited by 276 · see citing works
Activatable Polymer Nanoenzymes for Photodynamic Immunometabolic Cancer Therapy
Zeng, Z., Zhang, C., Li, J., Cui, D., Jiang, Y., & Pu, K. (2021) · Advanced Materials · doi:10.1002/adma.202007247 · Cited by 276 · see citing works
Lv, Z., Wei, H., Li, Q. F., Su, X., Liu, S., Zhang, K. Y., Lv, W. Y., Zhao, Q., Li, X., & Huang, W. (2017) · Chemical Science · doi:10.1039/c7sc03765a · Cited by 269 · see citing works
Wente, S. R. (2000) · Science · doi:10.1126/science.288.5470.1374 · Cited by 258 · see citing works
Photoactivatable Protherapeutic Nanomedicine for Cancer
Zhang, Y., Xu, C., Yang, X., & Pu, K. (2020) · Advanced Materials · doi:10.1002/adma.202002661 · Cited by 240 · see citing works
Aggregation-Induced Emission Photosensitizers: From Molecular Design to Photodynamic Therapy
Dai, J., Wu, X., Ding, S., Lou, X., Xia, F., Wang, S., & Hong, Y. (2020) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.9b02014 · Cited by 238 · see citing works
Qin, W., Li, K., Feng, G., Li, M., Yang, Z., Liu, B., & Tang, B. Z. (2013) · Advanced Functional Materials · doi:10.1002/adfm.201302114 · Cited by 227 · see citing works
Self-citationOrganic Photodynamic Nanoinhibitor for Synergistic Cancer Therapy
Jiang, Y., Li, J., Zeng, Z., Xie, C., Lyu, Y., & Pu, K. (2019) · Angewandte Chemie International Edition · doi:10.1002/anie.201903968 · Cited by 220 · see citing works
Highly efficient conversion of superoxide to oxygen using hydrophilic carbon clusters
Samuel, E. L. G., Marcano, D. C., Berka, V., Bitner, B. R., Wu, G., Potter, A., Fabian, R. H., Pautler, R. G., Kent, T. A., Tsai, A.-L., et al. (2015) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1417047112 · Cited by 214 · see citing works
Xu, W., Lee, M. M. S., Nie, J., Zhang, Z., Kwok, R. T. K., Lam, J. W. Y., Xu, F., Wang, D., & Tang, B. Z. (2020) · Angewandte Chemie International Edition · doi:10.1002/anie.202000740 · Cited by 192 · see citing works
Self-citationYan, J., Kim, Y. S., Yang, X.-P., Li, L., Liao, G., Xia, F., & Jetten, A. M. (2007) · Cancer Research · doi:10.1158/0008-5472.can-07-0924 · Cited by 170 · see citing works
Gilson, R. C., Black, K. C. L., Lane, D. D., & Achilefu, S. A. (2017) · Angewandte Chemie International Edition · doi:10.1002/anie.201704458 · Cited by 169 · see citing works
García-Díaz, M., Huang, Y., & Hamblin, M. R. (2016) · Methods · doi:10.1016/j.ymeth.2016.06.025 · Cited by 168 · see citing works
Zhang, X., Xu, X., Li, Y., Hu, C., Zhang, Z., & Gu, Z. (2018) · Advanced Materials · doi:10.1002/adma.201707240 · Cited by 133 · see citing works
Self-citationSubcellular, Time-Resolved Studies of Singlet Oxygen in Single Cells
Snyder, J. W., Skovsen, E., Lambert, J. D. C., & Ogilby, P. R. (2005) · Journal of the American Chemical Society · doi:10.1021/ja055342p · Cited by 115 · see citing works
Li, Y., Tang, R., Liu, X., Gong, J., Zhao, Z., Sheng, Z., Zhang, J., Li, X., Niu, G., Kwok, R. T. K., et al. (2020) · ACS Nano · doi:10.1021/acsnano.0c05610 · Cited by 104 · see citing works
Self-citationSide effects of hyperbaric oxygen therapy.
Camporesi, E. M. (2014) · PubMed · Cited by 96 · see citing works
Robust and Long-Lived Excited State Ru(II) Polyimine Photosensitizers Boost Hydrogen Production
Guo, S., Chen, K., Dong, R., Zhang, Z., Zhao, J., & Lu, T. (2018) · ACS Catalysis · doi:10.1021/acscatal.8b02226 · Cited by 94 · see citing works
Self-citationLi, Y., Ren, T., & Dong, W. (2012) · Journal of Photochemistry and Photobiology A Chemistry · doi:10.1016/j.jphotochem.2012.10.002 · Cited by 79 · see citing works
Wang, J., Hou, Y., Lei, W., Zhou, Q., Li, C., Zhang, B., & Wang, X. (2012) · ChemPhysChem · doi:10.1002/cphc.201200224 · Cited by 76 · see citing works
Chowdhury, G., Junnotula, V., Daniels, J. S., Greenberg, M. M., & Gates, K. S. (2007) · Journal of the American Chemical Society · doi:10.1021/ja074432m · Cited by 57 · see citing works
Direct Strand Scission from a Nucleobase Radical in RNA
Jacobs, A. C., Resendiz, M. J. E., & Greenberg, M. M. (2010) · Journal of the American Chemical Society · doi:10.1021/ja100281x · Cited by 56 · see citing works
Li, Q., Huang, C., Liu, L., et al. (2018) · Cytometry Part A · doi:10.1002/cyto.a.23596 · Cited by 52 · see citing works
Hyperbaric oxygen promotes malignant glioma cell growth and inhibits cell apoptosis
Wang, Y., Zhan, Y. P., Pan, S., et al. (2015) · Oncology Letters · doi:10.3892/ol.2015.3244 · Cited by 42 · see citing works
Wu, H., Wang, Y., Qiao, X., Wang, D., Yang, X., & Li, H. (2018) · Chemistry of Materials · doi:10.1021/acs.chemmater.8b01791 · Cited by 40 · see citing works
Self-citationPhotosensitization by the trypanocidal agent crystal violet. Type i versus type II reactions
Reszka, K. J., Cruz, F. S., & Docampo, R. (1986) · Chemico-Biological Interactions · doi:10.1016/s0009-2797(86)80095-3 · Cited by 29 · see citing works
Flagged first, then by citations
Research works printed but not linked: 9
- [15]E. M. Camporesi, Undersea Hyperbaric Med. 2014, 41, 253. 24984321
- [30]R. Bonnett, Chem. Soc. Rev. 1995, 24, 19.
- [34]M. Kang, Z. Zhang, N. Song, M. Li, P. Sun, X. Chen, D. Wang, B. Z. Tang, Aggregate 2020, 1, 80.
- [37]Q. Wan, R. Zhang, Z. Zhuang, Y. Li, Y. Huang, Z. Wang, W. Zhang, J. Hou, B. Z. Tang, Adv. Funct. Mater. 2020, 30, 2002057.
- [47]A. Weller, Z. Phys. Chem. 1982, 133, 93.
- [48]S. Guo, K. K. Chen, R. Dong, Z. M. Zhang, J. Zhao, T. B. Lu, ACS Catal. 2018, 8, 8659.
- [59]Y. Li, T. Ren, W. J. Dong, J. Photochem. Photobiol., A 2013, 251, 1.
- [60]W. Qin, K. Li, G. Feng, M. Li, Z. Yang, B. Liu, B. Z. Tang, Adv. Funct. Mater. 2014, 24, 635.
- [61]H. Wu, Y. Wang, X. Qiao, D. Wang, X. Yang, H. Li, Chem. Mater. 2018, 30, 6992.
Cited by
Sorted by citations
The fast-growing field of photo-driven theranostics based on aggregation-induced emission
Zhang, Z., Kang, M., Tan, H., Song, N., Li, M., Xiao, P., Yan, D., Zhang, L., Wang, D., & Tang, B. Z. (2022) · Chemical Society Reviews · doi:10.1039/d1cs01138c · Cited by 374 · see citing works
Self-citationBarman, D., Narang, K., Parui, R., Zehra, N., Khatun, M. N., Adil, L. R., & Iyer, P. K. (2022) · Aggregate · doi:10.1002/agt2.172 · Cited by 113 · see citing works
- Authors
- Kang, M., Zhang, Z., Xu, W., Wen, H., Zhu, W., Wu, Q., Wu, H., Gong, J., Wang, Z., Wang, D., & Tang, B. Z.
- Affiliations
- Shenzhen University (CN)
- Hong Kong University of Science and Technology (HK)
- Dalian University of Technology (CN)
- Corresponding author
- Wang, Dong
- Tang, Ben Zhong
- ORCID
- Venue
- Advanced Science
- Publisher
- Wiley
- Published
- 2021-05-21
- Volume
- 8
- Issue
- 14
- Pages
- e2100524-e2100524
- ISSN
- 2198-3844 (ISSN-L)
- PMC
- PMC8292883
- OpenAlex
- W3161337988
- Cited by
- 193
- References
- 62
- Citations by year
- 2026: 15 · 2025: 35 · 2024: 59 · 2023: 40 · 2022: 38 · 2021: 6
- FWCI
- 23.21
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Advanced Science (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Rare & Special e-Zone (The Hong Kong University of Science and Technology) (submittedVersion)
- Funders
- National Natural Science Foundation of China (51903163, 21801169)
- Topics
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Photodynamic Therapy Research Studies
- Physical Sciences › Engineering › Biomedical Engineering › Nanoplatforms for cancer theranostics
- Physical Sciences › Materials Science › Materials Chemistry › Luminescence and Fluorescent Materials
- Keywords
- photodynamic therapy, type I photosensitizers, aggregation-induced emission, nuclear targeting, reactive oxygen species, TAT peptide, polymeric nanoparticles, tetraphenylethylene, singlet-triplet energy gap, cancer therapy
- MeSH terms
- Animals, Cell Survival, Disease Models, Animal, Fluorescence, Male, Mice, Inbred BALB C, Neoplasms, Photochemotherapy, Polymers, Photosensitizing Agents, Reactive Oxygen Species, Cell Line, Tumor, Mice
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
