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Microneedles loaded with glutathione-scavenging composites for nitric oxide enhanced photodynamic therapy of melanoma
Bioengineering & Translational Medicine ( IF 6.1 ) Pub Date : 2022-06-10 , DOI: 10.1002/btm2.10352
Fan Jia 1 , Weijiang Yu 1 , Xinfang Li 1 , Yonghang Chen 1 , Youxiang Wang 1 , Jian Ji 1
Affiliation  

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材料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)代表了一种有吸引力且有前景的黑色素瘤治疗途径。然而,其治疗效果因药物输送效率低和癌细胞中谷胱甘肽 (GSH) 水平高而受到影响。为了克服这些挑战,人们提出了加载 GSH 清除纳米复合材料的微针 (MN) 系统,用于一氧化氮 (NO) 增强的 PDT。该纳米复合材料由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 MN 后,G 4 -SNAP/Ce6 复合材料可快速输送,并通过 GSH 消耗和活性氮生成,显着增强 PDT 期间的治疗效果。即使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癌症消融效果比单独使用 Ce6 更好。该策略可能会激发未来皮肤肿瘤 PDT 相关治疗的新思路。
更新日期:2022-06-10
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