In Situ Secondary Self‐Assembly of Near‐Infrared II J‐Aggregates: A Novel Phototheranostic Strategy for Inducing Tumor Pyroptosis
Abstract
Pyroptosis, a programmed cell death mechanism that bypasses apoptosis resistance and triggers tumor‐specific immune responses, has gained much attention as a promising approach to cancer therapy. Despite enhancing tumor accumulation and extending the circulation of small‐molecule drugs, nanomedicines still face significant challenges, including poor tissue penetration, tumor resistance, and hypoxic microenvironments. To overcome these challenges, a novel near‐infrared II (NIR‐II) J‐aggregate‐based nanomedicine is designed, leveraging an in situ secondary self‐assembly strategy to fabricate highly targeted nanoparticles (MSDP NPs). These nanomedicines trigger pyroptosis by generating type I reactive oxygen species, especially superoxide anions, while simultaneously activating photoimmunotherapy. In vivo studies demonstrate that MSDP NPs achieve efficient tumor penetration and prolong tumor retention, which is facilitated by the J‐aggregate‐driven formation of microscale spindle‐shaped fibrillar bundles through in situ secondary self‐assembly at the tumor site. This unique structural transformation enhances nanomedicine accumulation in tumor tissues, enabling robust NIR‐II fluorescence imaging and improving therapeutic efficacy even in hypoxic tumor microenvironments. This study provides an innovative phototheranostic strategy that utilizes the in situ secondary self‐assembly of NIR‐II J‐aggregates to induce tumor pyroptosis, offering a potential solution to the limitations of current nanomedicines in cancer therapy.
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The structural features of cyano-based fluorophores impart AIE characteristics, endowing the resulting AIE nanoparticles with high generality and extended emission wavelengths.
“These structural features also impart AIE characteristics, endowing the resulting AIE nanoparticles with high generality and extended emission wavelengths191.”
From Organic small-molecule NIR-II fluorophores for tumor phototheranostics (2026) · cites this paper as [191]
Cyano derivatives such as malononitrile are essential electron acceptors for designing NIR-II fluorescent probes.
“Cyano derivatives, such as malononitrile, are essential electron acceptors for designing NIR-II fluorescent probes”
From Organic small-molecule NIR-II fluorophores for tumor phototheranostics (2026) · cites this paper as [191]
Li et al. developed a cyano-based donor-π-acceptor photosensitizer M featuring triphenylamine donor and 1,3-bis(dicyanomethylene)indane acceptor.
“Li et al. developed a cyano-based donor-π-acceptor photosensitizer (M), featuring triphenylamine (donor) and 1,3-bis(dicyanomethylene)indane (acceptor) (Fig. 12b)191.”
From Organic small-molecule NIR-II fluorophores for tumor phototheranostics (2026) · cites this paper as [191]
M self-assembly into J-aggregates led to a ~30 nm red-shift in absorption (from 681 nm to 710 nm), yielding strong NIR-II emission that reached 1350 nm.
“Its self-assembly into J-aggregates led to a ~ 30 nm red-shift in absorption (from 681 nm to 710 nm), yielding strong NIR-II emission that reached 1350 nm.”
From Organic small-molecule NIR-II fluorophores for tumor phototheranostics (2026) · cites this paper as [191]
In aqueous solution, M tended to self-assemble into J-aggregates exhibiting remarkable NIR-II emission, with the emission wavelength extending up to 1350 nm.
“In aqueous solution, M tended to self-assemble into J-aggregates exhibiting remarkable NIR-II emission, with the emission wavelength extending up to 1350 nm.”
From Organic small-molecule NIR-II fluorophores for tumor phototheranostics (2026) · cites this paper as [191]
Through the combination of chemotherapy and phototherapy, MSDP NPs significantly inhibited tumor growth and activated anti-tumor immune responses.
“Through the combination of chemotherapy and phototherapy, MSDP NPs significantly inhibited tumor growth and activated anti-tumor immune responses.”
From Organic small-molecule NIR-II fluorophores for tumor phototheranostics (2026) · cites this paper as [191]
Under 660 nm laser irradiation, MSDP NPs demonstrated a high PCE of 45.21% and triggered pyroptosis of HepG2 cells via the generation of Type-I ROS.
“Under 660 nm laser irradiation, MSDP NPs demonstrated a high PCE of 45.21% and triggered pyroptosis of HepG2 cells via the generation of Type-I ROS.”
From Organic small-molecule NIR-II fluorophores for tumor phototheranostics (2026) · cites this paper as [191]
MSDP NPs achieved efficient tumor penetration and sustained retention through in situ secondary self-assembly, enabling clear visualization of murine vascular structures under NIR-II imaging.
“Furthermore, MSDP NPs successfully achieved efficient tumor penetration and sustained retention through in situ secondary self-assembly, enabling clear visualization of murine vascular structures under NIR-II imaging.”
From Organic small-molecule NIR-II fluorophores for tumor phototheranostics (2026) · cites this paper as [191]
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Self-citationSu, M., Zhang, L., Kong, D., Liu, H., Zhou, Y., Li, X., Wang, Z., Wang, H., Luo, S., Xu, Y., et al. (2026) · Advanced Functional Materials · doi:10.1002/adfm.78355
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Self-citationA Synergistic Sonosensitive Pyroptosis Nanoactivator for Efficient Lung Adenocarcinoma Therapy
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Hypoxia‐Tolerant Supramolecular Nanomicelles for Pyroptosis‐Enhanced NIR‐II Phototheranostics
Wang, X., Dong, K., Wang, Z., Tang, Y., & Li, Q. (2026) · Advanced Materials · doi:10.1002/adma.75395
Self-citationPeptidomimetic Polymer With Conformation‐Coded Hierarchical Assembly for Visualizing Biodistribution
Zhou, Y., Li, S., Yang, D., Wang, Y., Zou, J., Wang, M., Peng, C., Liu, Y., Tan, H. S., & Ding, M.-M. (2026) · Angewandte Chemie · doi:10.1002/ange.1895737
Peptidomimetic Polymer With Conformation‐Coded Hierarchical Assembly for Visualizing Biodistribution
Zhou, Y., Li, S., Yang, D., Wang, Y., Zou, J., Wang, M., Peng, C., Liu, Y., Tan, H. S., & Ding, M.-M. (2026) · Angewandte Chemie International Edition · doi:10.1002/anie.1895737
- Authors
- Tang, Y., Xiang, D., & Li, Q.
- Affiliations
- Southeast University (CN)
- Kent State University (US)
- Corresponding author
- Li, Quan
- ORCID
- Venue
- Advanced Materials
- Publisher
- Wiley
- Published
- 2025-04-21
- Volume
- 37
- Issue
- 27
- Pages
- e2501184-e2501184
- ISSN
- 0935-9648 (ISSN-L)
- 1521-4095
- OpenAlex
- W4409691790
- Cited by
- 48
- References
- 49
- Citations by year
- 2026: 26 · 2025: 22
- FWCI
- 11.63
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Advanced Materials (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Fundamental Research Funds for the Central Universities
- Topics
- Physical Sciences › Engineering › Biomedical Engineering › Nanoplatforms for cancer theranostics
- Physical Sciences › Materials Science › Materials Chemistry › Luminescence and Fluorescent Materials
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Photodynamic Therapy Research Studies
- Keywords
- pyroptosis, phototheranostics, photodynamic therapy, reactive oxygen species, superoxide, photoimmunotherapy, tumor hypoxia, NIR-II fluorescence imaging, tumor penetration, tumor retention, cancer nanomedicine
- MeSH terms
- Theranostic Nanomedicine, Pyroptosis, Animals, Humans, Infrared Rays, Neoplasms, Reactive Oxygen Species, Cell Line, Tumor, Mice, Nanoparticles, Tumor Microenvironment
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