Citation: 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[J]. Chinese Chemical Letters, ;2025, 36(12): 110908. doi: 10.1016/j.cclet.2025.110908 shu

Dissolving microneedle-assisted in situ cancer vaccine combined with cytolytic peptide for anti-melanoma immunotherapy

Ying Sun ^{a, 1} ,
Minglong Chen ^{b, 1} ,
Ying Chen ^{c, 1} ,
Wanchen Zhao ^c ,
Yanping Fu ^c ,
Zhengwei Huang ^c ,
Chao Lu ^c ,
Chuanbin Wu ^c ,
Xin Pan ^a ,
Guilan Quan ^{c, *,}

a.
School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006, China
b.
Department of Pharmacy, The First Affiliated Hospital of University of Science and Technology of China, and Laboratory of Precision and Intelligent Chemistry, Department of Polymer Science and Engineering, University of Science and Technology of China, Hefei 230026, China
c.
College of Pharmacy, Jinan University, Guangzhou 511443, China

quanguilan@jnu.edu.cn

Received Date: 17 October 2024
Revised Date: 27 January 2025
Accepted Date: 1 February 2025
Available Online: 2 February 2025

Figures(6)

Cancer vaccines are a notable area of immunotherapy due to their capacity to elicit specific antitumor immune responses and to create immune memory. However, they encounter challenges in clinical practice due to several bottlenecks, including tumor heterogeneity, low immunogenicity, immunosuppressive tumor environment, and delivery obstacles, which collectively impact their clinical effectiveness. In this study, we developed nanocomposites containing positively charged melittin (MEL) and negatively charged photosensitizer indocyanine green (ICG), embedded in dissolving microneedles (MEL/ICG-HA@DMNs). This approach allows precise drug delivery by creating microchannels that bypass the stratum corneum barrier, targeting superficial lesions directly. Our results demonstrated that the complexation of MEL and ICG significantly reduced the hemolytic activity of MEL while maintaining its ability to disrupt cell membranes. After loading MEL/ICG-HA into the microneedle, MEL/ICG-HA@DMNs not only effectively concentrated the drug at the tumor site, inducing localized hyperthermia and successfully ablating the tumor, but also formed an in situ whole-cell vaccine containing a rich source of tumor-associated antigens. Moreover, the system promoted dendritic cell maturation and increased the M1/M2 macrophage ratio, enhancing the immune response. By overcoming the limitations of traditional cancer vaccines, this system ensures precise drug delivery and robust immune activation. This innovative approach holds the potential to revolutionize cancer treatment, offering a new paradigm in precision oncology.
- Photoimmunotherapy,
- Dissolving microneedle,
- Melittin,
- In situ cancer vaccine,
- Immunomodulation
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