NIR Enhanced pH-Responsive Microneedles for Synergetic Therapy of Melanoma.

IF 3.6 4区医学 Q2 CHEMISTRY, MEDICINAL ChemMedChem Pub Date : 2024-09-30 DOI:10.1002/cmdc.202400537

Weiqiang Han, Lan Yu, Zhuo Liu, Chaofan Wang, Qi Zhang, Yongqian Xu, Hongjuan Li, Fengyu Liu, Shiguo Sun

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Abstract

Melanoma has emerged as a significant threat to human life and health. Microneedle (MN)-mediated transdermal drug delivery (TDD) has garnered attention in melanoma treatment for bypassing the first-pass effect. However, the propensity of melanoma to metastasize presents substantial challenges for MN mediated local treatment. Developing systemic therapies, such as immunotherapy in combination with TDD, is crucial for achieving effective melanoma treatment. Herein, a polyvinyl alcohol (PVA) MN-mediated multifunctional TDD system, designated MN@PDA@1-MT/CUR/DOX@HA (MN@PMCDH), was developed for synergetic chemotherapy/photothermal/immunotherapy of melanoma. PMCDH nanomedicines penetrate deep skin layers through MNs, accumulate at tumor sites guided by hyaluronic acid (HA), and selectively release drugs in response to the acidic tumor microenvironment and near-infrared (NIR) stimulation. Released curcumin (CUR) significantly enhances the efficacy of photothermal therapy (PTT) and chemotherapy, as well as improves the induction of immunogenic cell death (ICD) by increasing melanoma sensitivity to polydopamine (PDA)-mediated photothermal effects and doxorubicin (DOX). Moreover, the incorporation of 1-methyltryptophan (1-MT) to reverse the tumor immunosuppressive microenvironment can further enhance the effects of immunotherapy. In vitro studies revealed that the MN@PMCDH system can effectively induce ICD and inhibit tumor cell growth. Additionally, remarkable deep tumor cell inhibition effects are also achieved in 3D tumor models.

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用于黑色素瘤协同治疗的近红外增强型 pH 响应微针

黑色素瘤已成为威胁人类生命和健康的重大疾病。微针（MN）介导的透皮给药（TDD）可绕过首过效应，在黑色素瘤治疗中备受关注。然而，黑色素瘤的转移倾向给微针介导的局部治疗带来了巨大挑战。开发全身性疗法，如结合 TDD 的免疫疗法，对于实现黑色素瘤的有效治疗至关重要。在此，我们开发了一种聚乙烯醇（PVA）MN介导的多功能TDD系统，命名为MN@PDA@1-MT/CUR/DOX@HA（MN@PMCDH），用于黑色素瘤的协同化疗/光热/免疫治疗。PMCDH 纳米药物通过 MNs 穿透皮肤深层，在透明质酸（HA）的引导下聚集在肿瘤部位，并在酸性肿瘤微环境和近红外（NIR）刺激下选择性释放药物。释放的姜黄素（CUR）能显著提高光热疗法（PTT）和化疗的疗效，并通过提高黑色素瘤对多巴胺（PDA）介导的光热效应和多柔比星（DOX）的敏感性，改善免疫原性细胞死亡（ICD）的诱导。此外，加入 1-甲基色氨酸（1-MT）以逆转肿瘤免疫抑制微环境还能进一步增强免疫疗法的效果。体外研究显示，MN@PMCDH 系统能有效诱导 ICD 并抑制肿瘤细胞生长。此外，在三维肿瘤模型中也取得了显著的深层肿瘤细胞抑制效果。

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来源期刊

ChemMedChem 医学-药学

CiteScore

6.70

自引率

2.90%

发文量

280

审稿时长

1 months

期刊介绍： Quality research. Outstanding publications. With an impact factor of 3.124 (2019), ChemMedChem is a top journal for research at the interface of chemistry, biology and medicine. It is published on behalf of Chemistry Europe, an association of 16 European chemical societies. ChemMedChem publishes primary as well as critical secondary and tertiary information from authors across and for the world. Its mission is to integrate the wide and flourishing field of medicinal and pharmaceutical sciences, ranging from drug design and discovery to drug development and delivery, from molecular modeling to combinatorial chemistry, from target validation to lead generation and ADMET studies. ChemMedChem typically covers topics on small molecules, therapeutic macromolecules, peptides, peptidomimetics, and aptamers, protein-drug conjugates, nucleic acid therapies, and beginning 2017, nanomedicine, particularly 1) targeted nanodelivery, 2) theranostic nanoparticles, and 3) nanodrugs. Contents ChemMedChem publishes an attractive mixture of: Full Papers and Communications Reviews and Minireviews Patent Reviews Highlights and Concepts Book and Multimedia Reviews.