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<p>Melanoma is a highly metastatic malignancy in which tumor-derived exosomes play critical roles in pre-metastatic niche formation and metastatic progression. However, most conventional therapeutic strategies primarily target primary tumor cells while overlooking metastasis-promoting exosomes. In this study, we developed a dual-targeting photothermal nanoplatform composed of Sambucus nigra agglutinin (SNA)-functionalized gold nanorods (SNA-AuNRs) capable of simultaneously recognizing melanoma cells and melanoma-derived exosomes through α-2,6 sialic acid targeting. SNA-AuNRs were synthesized by conjugating SNA lectin onto gold nanorods using PEGylation and EDC/NHS coupling chemistry, followed by physicochemical and biological characterization. The synthesized SNA-AuNRs retained strong near-infrared (NIR) absorbance and exhibited efficient photothermal conversion, reaching approximately 53&#xa0;°C under 850&#xa0;nm NIR irradiation for 10&#xa0;min. In vitro studies demonstrated enhanced binding affinity of SNA-AuNRs toward melanoma cells and melanoma-derived exosomes compared to normal cellular controls. Notably, SNA-AuNRs achieved approximately 51.3% binding efficiency toward melanoma-derived exosomes, representing an approximately 5.8-fold increase compared to normal cell-derived exosomes. Under NIR irradiation, SNA-AuNRs induced significant photothermal cytotoxicity in melanoma cells while maintaining high dark biocompatibility in normal cells. Furthermore, Transwell migration assays revealed that SNA-AuNRs effectively captured and anchored melanoma-derived exosomes, suggesting the formation of a sustained local chemoattractant gradient associated with enhanced cell migration. These findings suggest that SNA-AuNRs provide a promising dual-targeting photothermal strategy capable of simultaneously targeting melanoma cells and metastasis-associated exosomes for potential anti-metastatic therapy.</p>

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Dual-Targeted Photothermal Therapy of Melanoma and Pro-metastatic Exosomes Using Lectin-Functionalized Gold Nanorods

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年6月17日

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  • Jihyuk Yang,
  • Hyejun Ko,
  • Jiwon Kim,
  • Jaewoo Son,
  • Jaehee Jang,
  • Yonghyun Choi,
  • Minje Kim,
  • Masayoshi Tanaka,
  • Hee-Young Lee,
  • Jonghoon Choi

摘要

Melanoma is a highly metastatic malignancy in which tumor-derived exosomes play critical roles in pre-metastatic niche formation and metastatic progression. However, most conventional therapeutic strategies primarily target primary tumor cells while overlooking metastasis-promoting exosomes. In this study, we developed a dual-targeting photothermal nanoplatform composed of Sambucus nigra agglutinin (SNA)-functionalized gold nanorods (SNA-AuNRs) capable of simultaneously recognizing melanoma cells and melanoma-derived exosomes through α-2,6 sialic acid targeting. SNA-AuNRs were synthesized by conjugating SNA lectin onto gold nanorods using PEGylation and EDC/NHS coupling chemistry, followed by physicochemical and biological characterization. The synthesized SNA-AuNRs retained strong near-infrared (NIR) absorbance and exhibited efficient photothermal conversion, reaching approximately 53 °C under 850 nm NIR irradiation for 10 min. In vitro studies demonstrated enhanced binding affinity of SNA-AuNRs toward melanoma cells and melanoma-derived exosomes compared to normal cellular controls. Notably, SNA-AuNRs achieved approximately 51.3% binding efficiency toward melanoma-derived exosomes, representing an approximately 5.8-fold increase compared to normal cell-derived exosomes. Under NIR irradiation, SNA-AuNRs induced significant photothermal cytotoxicity in melanoma cells while maintaining high dark biocompatibility in normal cells. Furthermore, Transwell migration assays revealed that SNA-AuNRs effectively captured and anchored melanoma-derived exosomes, suggesting the formation of a sustained local chemoattractant gradient associated with enhanced cell migration. These findings suggest that SNA-AuNRs provide a promising dual-targeting photothermal strategy capable of simultaneously targeting melanoma cells and metastasis-associated exosomes for potential anti-metastatic therapy.