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负载谷胱甘肽清除复合物的微针用于一氧化氮增强的黑色素瘤光动力治疗

Microneedles loaded with glutathione-scavenging composites for nitric oxide enhanced photodynamic therapy of melanoma.

作者信息

Jia Fan, Yu Weijiang, Li Xinfang, Chen Yonghang, Wang Youxiang, Ji Jian

机构信息

MOE Key Laboratory of Macromolecule Synthesis and Functionalization of Ministry of Education, Department of Polymer Science and Engineering Zhejiang University Hangzhou Zhejiang China.

出版信息

Bioeng Transl Med. 2022 Jun 17;8(1):e10352. doi: 10.1002/btm2.10352. eCollection 2023 Jan.

DOI:10.1002/btm2.10352
PMID:36684091
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9842046/
Abstract

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 -nitroso--acrylate penicillamine (SNAP; a NO donor) grafted fourth-generation polyamide amine dendrimer (G) and chlorin e6 (Ce6). Upon local insertion of polyvinylpyrrolidone MNs, G-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 G-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.

摘要

光动力疗法(PDT)是一种治疗黑色素瘤的有吸引力且前景广阔的方法。然而,其治疗效果受到药物递送效率低下和癌细胞中高谷胱甘肽(GSH)水平的影响。为了克服这些挑战,提出了一种负载有GSH清除纳米复合材料的微针(MNs)系统,用于一氧化氮(NO)增强的PDT。该纳米复合材料由接枝到第四代聚酰胺胺树枝状大分子(G4)上的亚硝基丙烯酸青霉胺(SNAP;一种NO供体)和氯e6(Ce6)组成。通过局部插入聚乙烯吡咯烷酮微针,G-SNAP/Ce6复合材料能够快速递送,并在PDT过程中通过消耗GSH和产生活性氮物种显著增强治疗效果。即使单次给药和低功率光照,含有G-SNAP/Ce6的微针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。该策略可能为未来皮肤肿瘤的PDT相关治疗带来新的思路。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d96e/9842046/5c027837d980/BTM2-8-e10352-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d96e/9842046/9cfab62acfec/BTM2-8-e10352-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d96e/9842046/71c72a8f232c/BTM2-8-e10352-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d96e/9842046/24298279fa7f/BTM2-8-e10352-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d96e/9842046/54827340065a/BTM2-8-e10352-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d96e/9842046/a8c613d05f59/BTM2-8-e10352-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d96e/9842046/d1d51e178c81/BTM2-8-e10352-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d96e/9842046/5c027837d980/BTM2-8-e10352-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d96e/9842046/9cfab62acfec/BTM2-8-e10352-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d96e/9842046/71c72a8f232c/BTM2-8-e10352-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d96e/9842046/24298279fa7f/BTM2-8-e10352-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d96e/9842046/54827340065a/BTM2-8-e10352-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d96e/9842046/a8c613d05f59/BTM2-8-e10352-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d96e/9842046/d1d51e178c81/BTM2-8-e10352-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d96e/9842046/5c027837d980/BTM2-8-e10352-g002.jpg

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