Citation: Jing Li, Jie Wang, Bingqian Li, Meng Long, Xiumei Liu, Dengxuan Mao, Patrick Pan, Ying Liu, Zimei Wu, Yaqi Lyu, Nianping Feng. Engineering a garlic-derived nanovesicle/microneedle system to boost melanoma immunotherapy through self-amplifying cell death activation and immune remodelling[J]. Chinese Chemical Letters, ;2026, 37(8): 111878. doi: 10.1016/j.cclet.2025.111878 shu

Engineering a garlic-derived nanovesicle/microneedle system to boost melanoma immunotherapy through self-amplifying cell death activation and immune remodelling

Jing Li ^a ,
Jie Wang ^a ,
Bingqian Li ^a ,
Meng Long ^a ,
Xiumei Liu ^a ,
Dengxuan Mao ^a ,
Patrick Pan ^b ,
Ying Liu ^a ,
Zimei Wu ^{b, *,} ,
Yaqi Lyu ^{a, *,} ,
Nianping Feng ^{a, *,}

a.
School of Pharmacy, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China
b.
School of Pharmacy, Faculty of Medicine and Health Sciences, University of Auckland, Auckland 1023, New Zealand

z.wu@auckland.ac.nz

ylyu07@shutcm.edu.cn

npfeng@shutcm.edu.cn

Received Date: 25 June 2025
Revised Date: 21 September 2025
Accepted Date: 23 September 2025
Available Online: 24 September 2025

Figures(4)

Current immunotherapy for melanoma remains limited by low immunogenicity, immune-related toxicity, and an immunosuppressive tumor microenvironment (TME), necessitating more effective strategies to enhance treatment outcomes. Enhancing immunogenic cell death (ICD) induction with immune remodelling offers a promising approach to boost antitumor immunity. Here, we develop a transdermal microneedle (MN) system co-delivering garlic-derived nanovesicles (Ve) and immunomodulatory garlic polysaccharides (GP) to synergistically activate a self-reinforcing cell death pathway and reprogram the immunosuppressive TME. The dissolving MN platform enables efficient intratumoral delivery of Ve-fused thermosensitive liposomes (TSVL@PTX/ICG), loaded with paclitaxel (PTX) and the photosensitizer indocyanine green (ICG). Upon near-infrared (NIR) irradiation, ICG-mediated photothermal heating triggers rapid drug release, inducing pyroptosis via gasdermin E (GSDME) cleavage while amplifying photodynamic therapy (PDT)-driven mitochondrial damage. This dual cell death mechanism elicits robust ICD, releasing tumor antigens and damage-associated molecular patterns (DAMPs) to enhance dendritic cell activation and cytotoxic T-cell infiltration. Concurrently, GP reprograms tumor-associated macrophages (TAMs) from immunosuppressive M2 to pro-inflammatory M1 phenotypes, reshaping the TME into an immunostimulatory niche. This multi-modal approach, combining pyroptosis-driven ICD, PDT, and immune remodelling achieves potent antitumor immunity and melanoma suppression, highlighting the potential of plant-derived therapeutics in cancer immunotherapy.
- Garlic-derived nanovesicles,
- Dissolving microneedles,
- Pyroptosis,
- Immunotherapy,
- Melanoma
1. [1]
  J. Zhang, D. Huang, P.E. Saw, E. Song, Trends Immunol. 43 (2022) 523–545. doi: 10.3390/su15010523
2. [2]
  A.D. Waldman, J.M. Fritz, M.J. Lenardo, Nat. Rev. Immunol. 20 (2020) 651–668. doi: 10.1038/s41577-020-0306-5
3. [3]
  J. Naidoo, D.B. Page, B.T. Li, et al., Ann. Oncol. 26 (2015) 2375–2391. doi: 10.1093/annonc/mdv383
4. [4]
  G. Kroemer, C. Galassi, L. Zitvogel, Nat. Immunol. 23 (2022) 487–500. doi: 10.1038/s41590-022-01132-2
5. [5]
  B. Yu, Y. Wang, T. Bing, et al., Adv. Mater. 36 (2024) e2310456. doi: 10.1002/adma.202310456
6. [6]
  D.V. Krysko, A.D. Garg, A. Kaczmarek, et al., Nat. Rev. Cancer 12 (2012) 860–875. doi: 10.1038/nrc3380
7. [7]
  W. Qin, L. Qiao, Q. Wang, et al., ACS Nano 18 (2024) 1582–1598. doi: 10.1021/acsnano.3c09499
8. [8]
  K.N. Koch, M.L. Hartung, S. Urban, et al., J. Clin. Invest. 125 (2015) 3297–3302. doi: 10.1172/JCI79337
9. [9]
  R. Rouf, S.J. Uddin, D.K. Sarker, et al., Trends Food Sci. Technol. 104 (2020) 219–234. doi: 10.1016/j.tifs.2020.08.006
10. [10]
  T. Dilxat, Q. Shi, X. Chen, X. Liu, Aging 16 (2024) 6521–6536.
11. [11]
  X. Zhu, R. Lu, G. Zhang, et al., Biosci. Biotechnol. Biochem. 86 (2022) 1552–1561. doi: 10.1093/bbb/zbac149
12. [12]
  C. Xie, X. Zhou, W. Chen, et al., Chem. Biol. Interact. 397 (2024) 111083. doi: 10.1016/j.cbi.2024.111083
13. [13]
  J. Wu, G. Yu, X. Zhang, et al., Carbohydr. Polym. 344 (2024) 122530. doi: 10.1016/j.carbpol.2024.122530
14. [14]
  C. Yunna, H. Mengru, W. Lei, C. Weidong, Eur. J. Pharmacol. 877 (2020) 173090. doi: 10.1016/j.ejphar.2020.173090
15. [15]
  J. Xu, Y. Yu, Y. Zhang, et al., Nat. Nanotechnol. 19 (2024) 1569–1578. doi: 10.1038/s41565-024-01722-1
16. [16]
  T. Moniz, S.A. Costa Lima, S. Reis, Carbohydr. Polym. 266 (2021) 118098. doi: 10.1016/j.carbpol.2021.118098
17. [17]
  Z. Li, H. Lu, L. Fan, et al., Adv. Sci. 11 (2024) e2406942. doi: 10.1002/advs.202406942
18. [18]
  Y. Hu, Y. Miao, Y. Zhang, et al., ACS Nano 18 (2024) 27557–27569. doi: 10.1021/acsnano.4c08508
19. [19]
  Y. Ren, L. Mei, C. Huang, et al., ACS Mater. Lett. 5 (2023) 225–234. doi: 10.1021/acsmaterialslett.2c00867
20. [20]
  X. Sang, T. Gao, X. Liu, et al., Adv. Sci. 9 (2022) e2201834. doi: 10.1002/advs.202201834
21. [21]
  X. Liang, M. Mu, B. Chen, et al., Mater. Today Adv. 16 (2022) 100308. doi: 10.1016/j.mtadv.2022.100308
22. [22]
  Y. Wei, X. Cai, Q. Wu, et al., Bioengineering 10 (2023) 1199. doi: 10.3390/bioengineering10101199
23. [23]
  J. Lan, R. Zeng, Z. Li, et al., Adv. Mater. 36 (2024) e2408511. doi: 10.1002/adma.202408511
24. [24]
  R. Nordstrom, K.L. Browning, E. Parra-Ortiz, et al., J. Colloid Interface Sci. 562 (2020) 322–332. doi: 10.1016/j.jcis.2019.12.022
25. [25]
  C.G. Flores-Hernandez, J. Lopez-Barroso, B.A. Salazar-Cruz, et al., Polymers 16 (2024) 289. doi: 10.3390/polym16020289
26. [26]
  H. Chen, H. Xue, H. Zeng, et al., Biomater. Res. 27 (2023) 137. doi: 10.1186/s40824-023-00460-0
27. [27]
  Z. Sartawi, C. Blackshields, W. Faisal. J. Control Release 348 (2022) 186–205. doi: 10.1016/j.jconrel.2022.05.045
28. [28]
  H. Bian, D. Ma, X. Zhang, et al., Small 17 (2021) e2100398. doi: 10.1002/smll.202100398
29. [29]
  Y. Wang, W. Gao, X. Shi, et al., Nature 547 (2017) 99–103. doi: 10.1038/nature22393
30. [30]
  N. Zaffaroni, G.L. Beretta. Int. J. Mol. Sci. 24 (2023) 1285. doi: 10.3390/ijms24021285
31. [31]
  C. Rogers, D.A. Erkes, A. Nardone, et al., Nat. Commun. 10 (2019) 1689. doi: 10.1038/s41467-019-09397-2
32. [32]
  W. Li, X. Hu, S. Wang, et al., Int. J. Biol. Macromol. 145 (2020) 985–997. doi: 10.1016/j.ijbiomac.2019.09.189
33. [33]
  S. Zhang, Z. Li, X. Wang, et al., Carbohydr. Polym. 246 (2020) 116567. doi: 10.1016/j.carbpol.2020.116567
34. [34]
  Y. Wang, Q. Zhao, B. Zhao, et al., Adv. Sci. 9 (2022) e2105631. doi: 10.1002/advs.202105631
35. [35]
  P. Zheng, J. He, Y. Fu, et al., ACS Nano 18 (2024) 6863–6886. doi: 10.1021/acsnano.3c06987
36. [36]
  X. Dai, L. Lu, S. Deng, et al., Theranostics 10 (2020) 9332–9347. doi: 10.7150/thno.47137
37. [37]
  M.H. Orzalli, A. Prochera, L. Payne, et al., Immunity 54 (2021) 1447–1462. doi: 10.1016/j.immuni.2021.04.012
38. [38]
  K. Chen, H. Lin, X. Peng, et al., Chin. Chem. Lett. 36 (2025) 110045. doi: 10.1016/j.cclet.2024.110045
39. [39]
  Q. Wang, X. Ju, J. Wang, et al., Cancer Lett. 438 (2018) 17–23. doi: 10.1016/j.canlet.2018.08.028
40. [40]
  X. Liang, M. Mu, B. Chen, et al., Biomater. Res. 27 (2023) 120. doi: 10.3390/act12030120
41. [41]
  X. Li, F. Xiong, X. Cao, et al., Chin. Chem. Lett. 37 (2026) 110970. doi: 10.1016/j.cclet.2025.110970
42. [42]
  X.T. Liu, L.H. Chung, D. Liu, et al., Oncogenesis 11 (2022) 67. doi: 10.1038/s41389-022-00444-0
43. [43]
  X. Zhao, L.Y. Wang, J.M. Li, et al., Adv. Sci. 8 (2021) e2101498. doi: 10.1002/advs.202101498
44. [44]
  Z. Zheng, Y. Bian, Y. Zhang, G. Ren, G. Li, Cell Cycle 19 (2020) 1089–1104. doi: 10.1080/15384101.2020.1743911
45. [45]
  F. Yao, Z. Jin, Z. Zheng, et al., Cell Death Discov. 8 (2022) 112.
46. [46]
  A.C. Huang, R. Zappasodi, Nat. Immunol. 23 (2022) 660–670. doi: 10.1038/s41590-022-01141-1
47. [47]
  S. Kalaora, A. Nagler, J.A. Wargo, Y. Samuels, Nat. Rev. Cancer 22 (2022) 195–207. doi: 10.1038/s41568-022-00442-9
48. [48]
  C. Scirgolea, R. Sottile, M. De Luca, et al., Nat. Immunol. 25 (2024) 1845–1857. doi: 10.1038/s41590-024-01923-9
1. [1]
  Kaiyue Yang , Yifan Zhang , Shamei Luo , Chenxi Yu , Lin Chen , Qingyu Yu , Chenlu Huang , Guilei Ma , Linhua Zhang , Dunwan Zhu . Multifunctional nanoadjuvants-aided synergistic photothermal-immunotherapy of tumor. Chinese Chemical Letters, 2026, 37(4): 112324-. doi: 10.1016/j.cclet.2025.112324
2. [2]
  Zengzhen Chen , Lirong Zhao , Wenna Guo , Longfei Tan , Qiong Wu , Changhui Fu , Xiangling Ren , Shiping Yu , Xiaowei Chen , Nam-Young Kim , Guihua Jiang , Xianwei Meng . Microwave-sensitive Al-based nano-immunoadjuvant for strengthened tumor microwave-immunotherapy via programmed activation of NLRP3-mediated pyroptosis. Chinese Chemical Letters, 2026, 37(3): 111299-. doi: 10.1016/j.cclet.2025.111299
3. [3]
  Jia-Yin Su , Shiyao Song , Zi-Min Song , Xi Sun , Niangji Tsomo , Ying-Li Liu , Jingxuan Ma , Jie-Si Luo , Li-Na Wang , Suoyu Xiang , Cong Liang , Xue-Qun Luo , Jun Wu , Li-Bin Huang , Yan-Lai Tang . Arsenic trioxide-induced pyroptosis promotes the release of HMGB1 to activate natural killer cells related immunogenic cell death in leukemia. Chinese Chemical Letters, 2026, 37(7): 111585-. doi: 10.1016/j.cclet.2025.111585
4. [4]
  Ling Yang , Min Ren , Jie Wang , Liming He , Shanshan Wu , Shuai Yang , Wei Zhao , Hao Cheng , Xiaoming Zhou , Maling Gou . A non-viral gene therapy for melanoma by staphylococcal enterotoxin A. Chinese Chemical Letters, 2024, 35(5): 108822-. doi: 10.1016/j.cclet.2023.108822
5. [5]
  Dexuan Xiao , Tianyu Chen , Tianxu Zhang , Sirong Shi , Mei Zhang , Xin Qin , Yunkun Liu , Longjiang Li , Yunfeng Lin . Transdermal treatment for malignant melanoma by aptamer-modified tetrahedral framework nucleic acid delivery of vemurafenib. Chinese Chemical Letters, 2024, 35(4): 108602-. doi: 10.1016/j.cclet.2023.108602
6. [6]
  Zheyi Li , Xiaoyang Liang , Zitong Qiu , Zimeng Liu , Siyu Wang , Yue Zhou , Nan Li . Ion-interferential cell cycle arrest for melanoma treatment based on magnetocaloric bimetallic-ion sustained release hydrogel. Chinese Chemical Letters, 2024, 35(11): 109592-. doi: 10.1016/j.cclet.2024.109592
7. [7]
  Yang Liu , Jing Liang , Mengzhu Zheng , Haoze Song , Lixia Chen , Hua Li . PD-L1/SHP2 dual PROTACs inhibit melanoma by enhancing T-cell killing activity. Chinese Chemical Letters, 2025, 36(6): 110317-. doi: 10.1016/j.cclet.2024.110317
8. [8]
  Meng Sun , Jiazhen Yang , Leijiao Li , Yunhui Li , Wenliang Li , Jianxun Ding . Engineered bacteria potentiate cancer immunotherapy. Chinese Chemical Letters, 2025, 36(9): 111093-. doi: 10.1016/j.cclet.2025.111093
9. [9]
  Xue Ma , Anning Li , Zhiliang Gao , Ning Wang , Mengqi Li , Kanaparedu P.C. Sekhar , Muthupandian Ashokkumar , Shumei Zhai , Jiwei Cui , Qun Yu . Vaccination of STING agonists-loaded nanoemulsions for cancer immunotherapy. Chinese Chemical Letters, 2026, 37(6): 111410-. doi: 10.1016/j.cclet.2025.111410
10. [10]
  Liangliang Jia , Ye Hong , Xinyu He , Ying Zhou , Liujiao Ren , Hongjun Du , Bin Zhao , Bin Qin , Zhe Yang , Di Gao . Fighting hypoxia to improve photodynamic therapy-driven immunotherapy: Alleviating, exploiting and disregarding. Chinese Chemical Letters, 2025, 36(2): 109957-. doi: 10.1016/j.cclet.2024.109957
11. [11]
  Shuang Liang , Jianjun Yao , Dan Liu , Mengli Zhou , Yong Cui , Zhaohui Wang . Tumor-responsive covalent organic polymeric nanoparticles enhancing STING activation for cancer immunotherapy. Chinese Chemical Letters, 2025, 36(3): 109856-. doi: 10.1016/j.cclet.2024.109856
12. [12]
  Yuequan Wang , Congtian Wu , Chengcheng Feng , Qin Chen , Zhonggui He , Shenwu Zhang , Cong Luo , Jin Sun . Spatiotemporally-controlled supramolecular hybrid nanoassembly enabling ferroptosis-augmented photodynamic immunotherapy of cancer. Chinese Chemical Letters, 2025, 36(3): 109902-. doi: 10.1016/j.cclet.2024.109902
13. [13]
  Yanjun Cai , Yong Jiang , Yu Chen , Erzhuo Cheng , Yuan Gu , Yuwei Li , Qianqian Liu , Jian Zhang , Jifang Liu , Shisong Han , Bin Yang . Amplifying STING activation and immunogenic cell death by metal-polyphenol coordinated nanomedicines for enhanced cancer immunotherapy. Chinese Chemical Letters, 2025, 36(5): 110437-. doi: 10.1016/j.cclet.2024.110437
14. [14]
  Donghu Yu , Junneng Wang , Lei Hu , Youxian Wu , Tianqing Wang , Zhiyu Li , Zefen Wang , Qihang Ding , Yao Sun , Zhiqiang Li . Knowledge structures and research hotspots of immunotherapy for brain metastasis, glioma, meningioma, and pituitary adenoma: A bibliometric and visualization review. Chinese Chemical Letters, 2025, 36(12): 110995-. doi: 10.1016/j.cclet.2025.110995
15. [15]
  Xinlu Zhang , Yongxin Liu , Huan Li , Shutong Chen , Guocheng Wang , Xu Zhang , Chen Cao , Xiaoyuan Chen , Sheng Wang . A hypoxia-activated copper ion nanoexchanger for cancer immunotherapy by in situ precise production of immunogenic cell death inducer. Chinese Chemical Letters, 2026, 37(3): 111404-. doi: 10.1016/j.cclet.2025.111404
16. [16]
  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. Chinese Chemical Letters, 2026, 37(5): 111399-. doi: 10.1016/j.cclet.2025.111399
17. [17]
  Shi-Hao Wang , Qiu-Yi Duan , Rufeng Zhang , Zihao Wang , Zi-Xi Wang , Yang Shen , Fu-Gen Wu . A liquid PEG depot capable of triggering intratumoral O₂/H₂O₂ generation and neutralization/calcification for realizing light irradiation-free photodynamic therapy and immunotherapy. Chinese Chemical Letters, 2026, 37(8): 111772-. doi: 10.1016/j.cclet.2025.111772
18. [18]
  Ying Sun , Minglong Chen , Ying Chen , Wanchen Zhao , Yanping Fu , Zhengwei Huang , Chao Lu , Chuanbin Wu , Xin Pan , Guilan Quan . Dissolving microneedle-assisted in situ cancer vaccine combined with cytolytic peptide for anti-melanoma immunotherapy. Chinese Chemical Letters, 2025, 36(12): 110908-. doi: 10.1016/j.cclet.2025.110908
19. [19]
  Chenlu Huang , Xinyu Yang , Qingyu Yu , Linhua Zhang , Dunwan Zhu . Gas-generating polymersomes-based amplified photoimmunotherapy for abscopal effect and tumor metastasis inhibition. Chinese Chemical Letters, 2024, 35(6): 109680-. doi: 10.1016/j.cclet.2024.109680
20. [20]
  Junjie Wang , Yan Wang , Zhengdong Li , Changqiang Xie , Musammir Khan , Xingzhou Peng , Fabiao Yu . Triphenylamine-AIEgens photoactive materials for cancer theranostics. Chinese Chemical Letters, 2024, 35(6): 108934-. doi: 10.1016/j.cclet.2023.108934

Get Citation

PDF

XML

Metrics

PDF Downloads(0)
Abstract views(18)
HTML views(0)

通讯作者: 陈斌, bchen63@163.com

1.
沈阳化工大学材料科学与工程学院沈阳 110142