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用于黑色素瘤辅助治疗的丝蛋白制成的微粒

Microparticles Made with Silk Proteins for Melanoma Adjuvant Therapy.

作者信息

Trombino Sonia, Sole Roberta, Curcio Federica, Malivindi Rocco, Caracciolo Daniele, Mellace Silvia, Montagner Dino, Cassano Roberta

机构信息

Department of Pharmacy, Health and Nutritional Sciences, University of Calabria, Arcavacata di Rende, 87036 Cosenza, Italy.

Department of Experimental and Clinical Medicine, Magna Graecia University, 88100 Catanzaro, Italy.

出版信息

Gels. 2024 Jul 23;10(8):485. doi: 10.3390/gels10080485.

DOI:10.3390/gels10080485
PMID:39195014
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11353667/
Abstract

Melanoma is one of the most aggressive forms of skin cancer, which is characterized by metastasis and poor prognosis due to the limited effectiveness of current therapies and the toxicity of conventional drugs. For this reason and in recent years, one of the most promising strategies in the treatment of this form of cancer is the use of drug delivery systems as carriers capable of conveying the therapeutic agent into the tumor microenvironment, thus preventing its degradation and improving its safety and effectiveness profiles. In the present work, microparticles based on silk fibroin and epifibroin 0039, silk-derived proteins loaded with idebenone, were created, which act as therapeutic carriers for topical use in the treatment of melanoma. The resulting particles have a spherical shape, good loading efficiency, and release capacity of idebenone. Efficacy studies have demonstrated a reduction in the proliferation of COLO-38, melanoma tumor cells, while safety tests have demonstrated that the microparticles are not cytotoxic and do not possess prosensitizing activity. Notably, transdermal release studies revealed that all particles released idebenone over more days. The analysis of the stimulatory markers of the proinflammatory process, CD54 and CD86, did not show any increase in expression, thus confirming the absence of potential prosesensitization effects of the silk fibroin-based particles. The research, therefore, found that idebenone-loaded silk protein microparticles could effectively reduce the proliferation of melanoma cells without cytotoxicity. This indicates the promise of a safe and effective treatment of melanoma.

摘要

黑色素瘤是最具侵袭性的皮肤癌形式之一,其特征在于转移以及由于当前疗法效果有限和传统药物毒性导致的预后不良。因此,近年来,治疗这种癌症形式最有前景的策略之一是使用药物递送系统作为载体,能够将治疗剂输送到肿瘤微环境中,从而防止其降解并改善其安全性和有效性。在本研究中,制备了基于丝素蛋白和表丝素蛋白0039的微粒,这两种丝源蛋白负载艾地苯醌,用作黑色素瘤治疗的局部用治疗载体。所得颗粒呈球形,具有良好的负载效率和艾地苯醌释放能力。功效研究表明,黑色素瘤肿瘤细胞COLO-38的增殖减少,而安全性测试表明微粒无细胞毒性且不具有致敏活性。值得注意的是,透皮释放研究表明,所有颗粒在数天内都能释放艾地苯醌。对促炎过程刺激标志物CD54和CD86的分析未显示表达增加,从而证实基于丝素蛋白的颗粒不存在潜在的致敏作用。因此,该研究发现负载艾地苯醌的丝蛋白微粒可有效降低黑色素瘤细胞的增殖且无细胞毒性。这表明黑色素瘤有望得到安全有效的治疗。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b4f8/11353667/d5a89ba4c0f7/gels-10-00485-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b4f8/11353667/48ec33a5fa49/gels-10-00485-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b4f8/11353667/a412c525cba0/gels-10-00485-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b4f8/11353667/a93897b729aa/gels-10-00485-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b4f8/11353667/95caf17339d9/gels-10-00485-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b4f8/11353667/3f813fe8fd42/gels-10-00485-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b4f8/11353667/1969cc0f6301/gels-10-00485-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b4f8/11353667/d5a89ba4c0f7/gels-10-00485-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b4f8/11353667/48ec33a5fa49/gels-10-00485-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b4f8/11353667/a412c525cba0/gels-10-00485-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b4f8/11353667/a93897b729aa/gels-10-00485-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b4f8/11353667/95caf17339d9/gels-10-00485-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b4f8/11353667/3f813fe8fd42/gels-10-00485-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b4f8/11353667/1969cc0f6301/gels-10-00485-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b4f8/11353667/d5a89ba4c0f7/gels-10-00485-g007.jpg

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Biomimetics (Basel). 2024 May 15;9(5):295. doi: 10.3390/biomimetics9050295.
2
Molecular Frontiers in Melanoma: Pathogenesis, Diagnosis, and Therapeutic Advances.黑色素瘤的分子前沿:发病机制、诊断及治疗进展
Int J Mol Sci. 2024 Mar 4;25(5):2984. doi: 10.3390/ijms25052984.
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Cutaneous melanoma.皮肤黑素瘤。
Lancet. 2023 Aug 5;402(10400):485-502. doi: 10.1016/S0140-6736(23)00821-8. Epub 2023 Jul 24.
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Microneedle-Assisted Topical Delivery of Idebenone-Loaded Bioadhesive Nanoparticles Protect against UV-Induced Skin Damage.载艾地苯醌的生物黏附纳米颗粒经微针辅助局部给药可预防紫外线引起的皮肤损伤。
Biomedicines. 2023 Jun 6;11(6):1649. doi: 10.3390/biomedicines11061649.
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Solid Lipid Nanoparticles Hydroquinone-Based for the Treatment of Melanoma: Efficacy and Safety Studies.基于对苯二酚的固体脂质纳米粒治疗黑色素瘤:疗效与安全性研究
Pharmaceutics. 2023 Apr 29;15(5):1375. doi: 10.3390/pharmaceutics15051375.
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