[P002] Poster

1:00 PM - 1:50 PM JST(4:00 AM - 4:50 AM UTC)

[P01-108] Papain-Ce6 Nanocluster-Loaded Dissolving Microneedles for Post-Surgical Melanoma Eradication and Wound Healing

○Ka-Young Lim¹, Taejung Kim¹, Jae-Young Lee¹ (1. Seoul National Univ. (Korea))

Keywords:

Papain nanocluster,Microneedle,Photodynamic therapy,Melanoma

[Purpose] Melanoma recurrence after surgical resection remains a critical challenge due to residual tumor cells at the wound margin. This study aimed to develop a dissolving microneedle (MN) patch incorporating a papain-Ce6 nanocluster (PCMN) for dual-action post-surgical therapy: photodynamic eradication of residual melanoma and promotion of wound healing. [Method] Papain-Ce6 (PC) nanoclusters were synthesized via EDC-NHS chemistry at molar ratios of 1:1 (PC1) and 1:2 (PC2), and characterized by DLS, TEM, MALDI-TOF, and UV-vis spectrophotometry. In vitro evaluations included ROS generation, cellular uptake, and cytotoxicity in B16F10 cells. Dissolving PCMN patches were fabricated using PVA as a matrix, and in vivo efficacy was assessed in both an allografted and a partial melanoma resection mouse model. [Results] PC1 showed an optimal size of 160.3 ± 1.60 nm with preserved protease activity (Vmax: 0.45 ± 0.06 μM/min), while PC2 formed large aggregates (1121 ± 25.05 nm) with markedly reduced enzymatic function. PC1 demonstrated effective singlet oxygen generation under 660 nm laser irradiation, enhanced cellular uptake over free Ce6, and potent laser-dependent cytotoxicity. In the allografted model, PCL significantly suppressed tumor growth (p < 0.001) without organ toxicity. In the partial resection model, the PCMN patch significantly reduced tumor volume and weight (p < 0.01). In the wound healing model, PCL achieved near-complete wound closure by day 12 (p < 0.05) with significantly reduced bacterial CFU counts (p < 0.01). [Consideration] The 1:1 molar ratio was critical for maintaining dual functionality, as excess Ce6 conjugation in PC2 caused protein aggregation and loss of proteolytic activity. The synergistic combination of PDT-mediated ROS generation and papain's intrinsic proteolytic and anti-inflammatory properties is anticipated to underlie the observed antitumor and wound healing effects.

[Conclusion] The PCMN patch offers a promising dual-action post-surgical platform for melanoma, simultaneously inhibiting tumor recurrence and accelerating wound healing. These findings support the translational potential of enzyme-photosensitizer conjugate-embedded microneedle systems as locally administered, multimodal therapeutics for post-surgical oncological management.