Photodynamic therapy (PDT) represents an attractive promising route for melanoma treatment. However, its therapeutic efficacy is compromised by inefficient drug delivery and high glutathione (GSH) levels in cancer cells. To overcome these challenges, microneedles (MNs) system loaded with GSH-scavenging nanocomposites was presented for nitric oxide (NO) enhanced PDT. The nanocomposites consisted of S-nitroso-N-acrylate penicillamine (SNAP; a NO donor) grafted fourth-generation polyamide amine dendrimer (G₄) and chlorin e6 (Ce6). Upon local insertion of polyvinylpyrrolidone MNs, G₄-SNAP/Ce6 composites were fast delivered and significantly amplified the therapeutic effects during PDT, via GSH depletion and reactive nitrogen species generation. Even with a single administration and low power light exposure, MNs with G₄-SNAP/Ce6 effectively halt the tumor progression. The system demonstrated better cancer ablation efficacy than Ce6 alone toward melanoma. The strategy may inspire new ideas for future PDT-related therapy for skin tumors.

中文翻译：

---

载有谷胱甘肽清除复合物的微针用于一氧化氮增强黑色素瘤的光动力治疗

光动力疗法 (PDT) 代表了黑色素瘤治疗的一种有吸引力的有前途的途径。然而，其治疗效果因药物输送效率低下和癌细胞中的高谷胱甘肽 (GSH) 水平而受到影响。为了克服这些挑战，载有 GSH 清除纳米复合材料的微针 (MNs) 系统被提出用于一氧化氮 (NO) 增强型 PDT。纳米复合材料由S -亚硝基 - N -丙烯酸酯青霉胺（SNAP；NO 供体）接枝的第四代聚酰胺胺树枝状聚合物 (G ₄ ) 和二氢卟酚 e6 (Ce6) 组成。在局部插入聚乙烯吡咯烷酮 MNs 后，G ₄-SNAP/Ce6 复合材料在 PDT 期间通过 GSH 耗竭和活性氮物质的产生快速传递并显着增强了治疗效果。即使采用单次给药和低功率光照，具有 G ₄ -SNAP/Ce6 的 MN 也能有效阻止肿瘤进展。该系统对黑色素瘤的消融效果优于单独使用 Ce6。该策略可能会激发未来皮肤肿瘤 PDT 相关疗法的新思路。