De Novo Design of Efficient NIR-II-Activated Heavy-Atom-Free Type-I Photosensitizer for Anti-Tumor Photoimmunotherapy

Huan Chen; Yu Wang; Zhangxin He; Yingpeng Wan; Chen Cao; Ziwei Lu; Yijian Gao; Xiao Cui; Ka-Wai Lee; Ji-Hua Tan; Wenchang Xu; Yuliang Yang; Xiliang Li; Yali Wang; Jianquan Hou; Shengliang Li; Chun-Sing Lee

doi:10.1002/adma.202501919

De Novo Design of Efficient NIR-II-Activated Heavy-Atom-Free Type-I Photosensitizer for Anti-Tumor Photoimmunotherapy

Huan Chen
, Yu Wang
, Zhangxin He
, Yingpeng Wan
, Chen Cao
, Ziwei Lu
, Yijian Gao
, Xiao Cui
, Ka-Wai Lee
, Ji-Hua Tan
, Wenchang Xu
, Yuliang Yang
, Xiliang Li
, Yali Wang^*
, Jianquan Hou
, Shengliang Li^*
, Chun-Sing Lee^*

^*Corresponding author for this work

Research output: Journal Publications and Reviews › RGC 21 - Publication in refereed journal › peer-review

28 Citations (Scopus)

Abstract

Type-I photosensitizers (PSs) are considered to be efficient agents for overcoming the oxygen-dependent deficiency of traditional photodynamic therapy (PDT). However, it is still challenging to design type-I PSs that can be activated by the second near-infrared (NIR-II) irradiation. Herein, a series of organic heavy-atom-free molecules are designed (named as CTU1, CTU2, and CTU3) and exhibit strong absorption bands over the first near-infrared and NIR-II regions. Among them, water-dispersible CTU3 nanoparticles (NPs) show strong J-aggregate characteristics and a good NIR-II absorption band, resulting in highly efficient •O₂⁻ generation upon irradiation of 1064 nm light. In addition, the CTU3 NPs also exhibit a high photothermal conversion efficiency of 88.6%. In vitro and in vivo experiments show that CTU3 NPs have superior PDT and photothermal therapy (PTT) effects, which can further induce immunogenic cell death and activate immune cells in 4T1 tumor-bearing mice for combined PDT/PTT anti-tumor photoimmunotherapy against refractory tumors. This work presents a paradigm of de novo design of NIR-II light-activated type-I PS for combinational photoimmunotherapy of cancer.

© 2025 Wiley-VCH GmbH

Original language	English
Article number	2501919
Number of pages	10
Journal	Advanced Materials
Volume	37
Issue number	33
Online published	4 Jun 2025
DOIs	https://doi.org/10.1002/adma.202501919
Publication status	Published - 21 Aug 2025

Funding

H.C., Y.W., and Z.H. contributed equally to this work. C.-S. Lee thanks the support of the Research Grants Council of Hong Kong Special Administrative Region and General Research Fund (Project No. 11318322). S. Li thanks the support of the National Natural Science Foundation of China (No. 52173135), the Natural Science Foundation of Jiangsu Province (BK20231523), the Jiangsu Specially Appointed Professorship, Leading Talents of Innovation and Entrepreneurship of Gusu (No. ZXL2022496), the Suzhou Science and Technology Program (No. SKY2022039), and Suzhou International Joint Laboratory for Diagnosis and Treatment of Brain Diseases.

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

SDG 3 Good Health and Well-being

Research Keywords

Heavy-atom-free
NIR-II-activated
Photoimmnuotherapy
Photosensitizer
Type-I PDT

Publisher's Copyright Statement

COPYRIGHT TERMS OF DEPOSITED POSTPRINT FILE: This is the peer reviewed version of the following article: Chen, H., Wang, Y., He, Z., Wan, Y., Cao, C., Lu, Z., Gao, Y., Cui, X., Lee, K.-W., Tan, J.-H., Xu, W., Yang, Y., Li, X., Wang, Y., Hou, J., Li, S., & Lee, C.- S. (2025). De Novo Design of Efficient NIR-II-Activated Heavy-Atom-Free Type-I Photosensitizer for Anti-Tumor Photoimmunotherapy. Advanced Materials, 37(33), Article 2501919., which has been published in final form at https://doi.org/10.1002/adma.202501919.
This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Use of Self-Archived Versions. This article may not be enhanced, enriched or otherwise transformed into a derivative work, without express permission from Wiley or by statutory rights under applicable legislation. Copyright notices must not be removed, obscured or modified. The article must be linked to Wiley’s version of record on Wiley Online Library and any embedding, framing or otherwise making available the article or pages thereof by third parties from platforms, services and websites other than Wiley Online Library must be prohibited

RGC Funding Information

RGC-funded

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10.1002/adma.202501919

305330298.pdfPost-print, 1.49 MB

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Chen, H., Wang, Y., He, Z., Wan, Y., Cao, C., Lu, Z., Gao, Y., Cui, X., Lee, K.-W., Tan, J.-H., Xu, W., Yang, Y., Li, X., Wang, Y., Hou, J., Li, S., & Lee, C.-S. (2025). De Novo Design of Efficient NIR-II-Activated Heavy-Atom-Free Type-I Photosensitizer for Anti-Tumor Photoimmunotherapy. Advanced Materials, 37(33), Article 2501919. https://doi.org/10.1002/adma.202501919

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title = "De Novo Design of Efficient NIR-II-Activated Heavy-Atom-Free Type-I Photosensitizer for Anti-Tumor Photoimmunotherapy",

abstract = "Type-I photosensitizers (PSs) are considered to be efficient agents for overcoming the oxygen-dependent deficiency of traditional photodynamic therapy (PDT). However, it is still challenging to design type-I PSs that can be activated by the second near-infrared (NIR-II) irradiation. Herein, a series of organic heavy-atom-free molecules are designed (named as CTU1, CTU2, and CTU3) and exhibit strong absorption bands over the first near-infrared and NIR-II regions. Among them, water-dispersible CTU3 nanoparticles (NPs) show strong J-aggregate characteristics and a good NIR-II absorption band, resulting in highly efficient •O2− generation upon irradiation of 1064 nm light. In addition, the CTU3 NPs also exhibit a high photothermal conversion efficiency of 88.6\%. In vitro and in vivo experiments show that CTU3 NPs have superior PDT and photothermal therapy (PTT) effects, which can further induce immunogenic cell death and activate immune cells in 4T1 tumor-bearing mice for combined PDT/PTT anti-tumor photoimmunotherapy against refractory tumors. This work presents a paradigm of de novo design of NIR-II light-activated type-I PS for combinational photoimmunotherapy of cancer. {\textcopyright} 2025 Wiley-VCH GmbH",

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AU - Chen, Huan

AU - Wang, Yu

AU - He, Zhangxin

AU - Wan, Yingpeng

AU - Cao, Chen

AU - Lu, Ziwei

AU - Gao, Yijian

AU - Cui, Xiao

AU - Lee, Ka-Wai

AU - Tan, Ji-Hua

AU - Xu, Wenchang

AU - Yang, Yuliang

AU - Li, Xiliang

AU - Wang, Yali

AU - Hou, Jianquan

AU - Li, Shengliang

AU - Lee, Chun-Sing

PY - 2025/8/21

Y1 - 2025/8/21

N2 - Type-I photosensitizers (PSs) are considered to be efficient agents for overcoming the oxygen-dependent deficiency of traditional photodynamic therapy (PDT). However, it is still challenging to design type-I PSs that can be activated by the second near-infrared (NIR-II) irradiation. Herein, a series of organic heavy-atom-free molecules are designed (named as CTU1, CTU2, and CTU3) and exhibit strong absorption bands over the first near-infrared and NIR-II regions. Among them, water-dispersible CTU3 nanoparticles (NPs) show strong J-aggregate characteristics and a good NIR-II absorption band, resulting in highly efficient •O2− generation upon irradiation of 1064 nm light. In addition, the CTU3 NPs also exhibit a high photothermal conversion efficiency of 88.6%. In vitro and in vivo experiments show that CTU3 NPs have superior PDT and photothermal therapy (PTT) effects, which can further induce immunogenic cell death and activate immune cells in 4T1 tumor-bearing mice for combined PDT/PTT anti-tumor photoimmunotherapy against refractory tumors. This work presents a paradigm of de novo design of NIR-II light-activated type-I PS for combinational photoimmunotherapy of cancer. © 2025 Wiley-VCH GmbH

AB - Type-I photosensitizers (PSs) are considered to be efficient agents for overcoming the oxygen-dependent deficiency of traditional photodynamic therapy (PDT). However, it is still challenging to design type-I PSs that can be activated by the second near-infrared (NIR-II) irradiation. Herein, a series of organic heavy-atom-free molecules are designed (named as CTU1, CTU2, and CTU3) and exhibit strong absorption bands over the first near-infrared and NIR-II regions. Among them, water-dispersible CTU3 nanoparticles (NPs) show strong J-aggregate characteristics and a good NIR-II absorption band, resulting in highly efficient •O2− generation upon irradiation of 1064 nm light. In addition, the CTU3 NPs also exhibit a high photothermal conversion efficiency of 88.6%. In vitro and in vivo experiments show that CTU3 NPs have superior PDT and photothermal therapy (PTT) effects, which can further induce immunogenic cell death and activate immune cells in 4T1 tumor-bearing mice for combined PDT/PTT anti-tumor photoimmunotherapy against refractory tumors. This work presents a paradigm of de novo design of NIR-II light-activated type-I PS for combinational photoimmunotherapy of cancer. © 2025 Wiley-VCH GmbH

KW - Heavy-atom-free

KW - NIR-II-activated

KW - Photoimmnuotherapy

KW - Photosensitizer

KW - Type-I PDT

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U2 - 10.1002/adma.202501919

DO - 10.1002/adma.202501919

M3 - RGC 21 - Publication in refereed journal

SN - 0935-9648

VL - 37

JO - Advanced Materials

JF - Advanced Materials

IS - 33

M1 - 2501919

ER -

De Novo Design of Efficient NIR-II-Activated Heavy-Atom-Free Type-I Photosensitizer for Anti-Tumor Photoimmunotherapy

Abstract

Funding

UN SDGs

Research Keywords

Publisher's Copyright Statement

RGC Funding Information

Access Output

Other Access Options

Permanent Link

Other Files and Links

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GRF: Conjugated Oligomer Nanoparticles for Type-I Photodynamic Therapy of Cancer with Near Infrared Radiation

Cite this

De Novo Design of Efficient NIR-II-Activated Heavy-Atom-Free Type-I Photosensitizer for Anti-Tumor Photoimmunotherapy

Abstract

Funding

UN SDGs

Research Keywords

Publisher's Copyright Statement

RGC Funding Information

Access Output

Other Access Options

Permanent Link

Other Files and Links

Fingerprint

Projects

GRF: Conjugated Oligomer Nanoparticles for Type-I Photodynamic Therapy of Cancer with Near Infrared Radiation

Cite this