Citation: Dongsheng Zhang, Tingting Wang, Cheng-Ao Li, Yi Tang, Fangyang Wang, Qiang Wang, Hongqing Li, Xun Zhang, Duo Sun, Yueying Zhang, Jiang Ming, Xiao Chen, Xiaolan Chen, Jingchao Li, Xinhui Su. Dual-gated delivery of melittin combined with moderate photothermal treatment using NIR-responsive Pd nanosheets for enhanced cancer immunotherapy[J]. Chinese Chemical Letters, ;2026, 37(5): 111399. doi: 10.1016/j.cclet.2025.111399 shu

Dual-gated delivery of melittin combined with moderate photothermal treatment using NIR-responsive Pd nanosheets for enhanced cancer immunotherapy

Dongsheng Zhang ^{a, 1} ,
Tingting Wang ^{a, 1} ,
Cheng-Ao Li ^{d, 1} ,
Yi Tang ^b ,
Fangyang Wang ^b ,
Qiang Wang ^b ,
Hongqing Li ^b ,
Xun Zhang ^a ,
Duo Sun ^b ,
Yueying Zhang ^b ,
Jiang Ming ^c ,
Xiao Chen ^{b, *,} ,
Xiaolan Chen ^{c, *,} ,
Jingchao Li ^{b, *,} ,
Xinhui Su ^{a, *,}

a.
PET Center, Department of Nuclear Medicine, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, China
b.
Department of Nuclear Medicine, Daping Hospital, Army Medical University, Chongqing 400042, China
c.
State Key Laboratory for Physical Chemistry of Solid Surfaces, Collaborative Innovation Center of Chemistry for Energy Materials, and Engineering Research Center for Nano-Preparation Technology of Fujian Province, College of Chemistry and Chemical Engineering Xiamen University, Xiamen 361005, China
d.
State Key Laboratory of Silicon and Advanced Semiconductor Materials, Institute for Composites Science Innovation, School of Materials Science and Engineering, Zhejiang University, Hangzhou 310058, China

xiaochen229@tmmu.edu.cn

chenxl@xmu.edu.cn

lijc@tmmu.edu.cn

suxinhui@zju.edu.cn

Received Date: 6 March 2025
Revised Date: 27 May 2025
Accepted Date: 29 May 2025
Available Online: 29 May 2025

Figures(5)

Immunotherapy has emerged as a promising strategy for combating tumor metastasis and recurrence, however, its efficacy is often hampered by the immunosuppressive tumor microenvironment (TME). The integration of nanomedicine-based photothermal therapy (PTT) with immunotherapy offers great potential to reshape the immune landscape, thereby enhancing immune responses and therapeutic outcomes. Nevertheless, conventional hyperthermia may induce heat-related damage and excessive inflammation in normal tissues. To address this challenge, we developed a novel therapeutic platform that combines tumor-specific delivery of melittin (MLT) with mild PTT using two-dimensional palladium nanosheets (Pd NSs). This approach allows for selective accumulation of MLT at tumor sites via the enhanced permeability and retention (EPR) effect and TME-responsive release, thereby maximizing antitumor efficacy while minimizing off-target toxicity. The resulting nanocomposite, MLT@Pd@PEG, exhibits excellent biocompatibility and efficient photothermal conversion under 808 nm laser irradiation. The acidic pH and localized heat in the TME synergistically trigger the controlled release of MLT, which disrupts cancer cell membranes and promotes tumor cell apoptosis. Moreover, this treatment facilitates the release of tumor-associated antigens and danger-associated molecular patterns (DAMPs), thereby activating cytotoxic T lymphocytes and natural killer (NK) cells. In vivo studies demonstrate that the combination of immune checkpoint blockade and MLT@Pd@PEG not only eradicates primary and distant tumors in bilateral tumor-bearing mouse models but also prevents tumor recurrence and metastasis by inducing durable immune memory. This comprehensive strategy integrating precise MLT delivery with mild PTT holds significant promise for advancing next-generation cancer immunotherapy.
- Melittin,
- Pd nanosheets,
- Drug delivery,
- Moderate photothermal therapy,
- Immunotherapy
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