4.4 Article

Photosensitizer-Free Phototherapy with Peptide Micelle Nanoadjuvants for Cancer Vaccine against Metastasis of Melanoma

Journal

ADVANCED THERAPEUTICS
Volume 4, Issue 8, Pages -

Publisher

WILEY
DOI: 10.1002/adtp.202000288

Keywords

melanin; melanoma; nanoadjuvant; peptide micelle; photosensitizer-free phototherapy

Funding

  1. National Research Foundation of Korea (NRF) - Ministry of Science and ICT, Republic of Korea [NRF-2021R1A2B5B03002123, NRF-2018R1A5A2024425]
  2. Korea Medical Device Development Fund - Korea government (the Ministry of Science and ICT) [9991007273, KMDF_PR_20200901_0106]
  3. Korean Health Technology R&D Project, Ministry of Health & Welfare, Republic of Korea [HI15C2842, HI18C2177, HI19C0664]
  4. Korea Medical Device Development Fund - Korea government (Ministry of Trade, Industry and Energy) [9991007273, KMDF_PR_20200901_0106]
  5. Korea Medical Device Development Fund - Korea government (Ministry of Health Welfare) [9991007273, KMDF_PR_20200901_0106]
  6. Korea Medical Device Development Fund - Korea government (Ministry of Food and Drug Safety) [9991007273, KMDF_PR_20200901_0106]

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This study reports a photosensitizer-free vaccination strategy for melanoma treatment, utilizing nanoadjuvants delivery. Melanin-enriched B16F10 melanoma cells exhibit strong photothermal effect under near-infrared light irradiation, inducing immunogenic cell death. The nanoadjuvant induces dendritic cell maturation and prevents lung melanoma nodule formation.
Here, an external photosensitizer-free vaccination strategy accompanied by delivery of nanoadjuvants is reported as a treatment for melanoma. Melanin-enriched B16F10 melanoma cells showed a strong and specific photothermal effect under irradiation of near-infrared (NIR) wavelength light, and a corresponding killing effect of cancer cells is observed. The irradiated melanoma cells exhibited surface exposure of the eat-me signal, calreticulin, which induced immunogenic cell death. The nanoadjuvant, which comprised imiquimod encapsulated in amphiphilic peptide-based micelles, induced dendritic cell maturation. In B16F10 melanoma tumor-bearing mice, irradiation of NIR light alone increased the temperature of the tumor site to 60 degrees C regardless of nanoadjuvant treatment. To mimic metastasis to sites near the primary tumor site, primary tumor-cured mice are rechallenged with B16F10 cells. In a lung metastasis model induced by intravenous injection of B16F10 cells, only nanoadjuvant-treated group showed significant prevention of B16F10 tumor nodule formation in the lung. The immunotherapeutic effects of this nanoadjuvant are supported by an observed increase of tumor-infiltrating CD8 + T cell populations. The results suggest that the combination of photosensitizer-free phototherapy with a peptide micelle nanoadjuvant has strong potential for clinical translation as a melanoma vaccine.

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