透皮纳米脂复合物同时抑制皮下黑色素瘤生长和抑制全身转移性黑色素瘤通过激活宿主免疫

IF 4.7 4区 医学 Q1 BIOTECHNOLOGY & APPLIED MICROBIOLOGY
Chia-Hung Chen PhD , Tzu-Han Weng MD , Cheng-Hsun Chuang PhD , Kai-Yao Huang PhD , Sih-Cheng Huang MSc , Pin-Rong Chen PhD , Hsiao-Hsuan Huang MSc , Ling-Ya Huang MSc , Pei-Chun Shen MSc , Po-Ya Chuang MSc , Hsiao-Yen Huang MSc , Yi-Syuan Wu MSc , Hao-Chiun Chang MD-PhD , Shun-Long Weng MD-PhD , Kuang-Wen Liao PhD
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引用次数: 2

摘要

经皮新辅助治疗可减少手术面积,提高免疫治疗效果。采用脂质体(lipoplex - peg - pei -complex, LPPC)包封阿霉素(DOX)并携带CpG低聚脱氧核苷酸;经皮给药的纳米脂质体药物复合物(LPPC-DOX-CpG)具有高细胞毒性和免疫刺激活性,可抑制黑色素瘤的全身转移。LPPC-DOX-CpG通过诱导肿瘤细胞凋亡和招募免疫细胞进入肿瘤区域,显著抑制皮下黑色素瘤的生长。动物实验进一步表明,经皮LPPC-DOX-CpG可抑制肝脏和肺部自发转移性黑色素瘤细胞的定植和生长。此外,NGS分析显示,通过触发IFN-γ和NF-κB通路募集和激活抗原呈递细胞和效应细胞,激活抗肿瘤反应是LPPC-DOX-CpG治疗效果的主要机制。最后,我们成功地证明了经皮LPPC-DOX-CpG作为一种有前途的渗透载体,可以激活全身抗肿瘤免疫,对抗皮下和转移性肿瘤。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

Transdermal nanolipoplex simultaneously inhibits subcutaneous melanoma growth and suppresses systemically metastatic melanoma by activating host immunity

Transdermal nanolipoplex simultaneously inhibits subcutaneous melanoma growth and suppresses systemically metastatic melanoma by activating host immunity

Benefit for clinical melanoma treatments, the transdermal neoadjuvant therapy could reduce surgery region and increase immunotherapy efficacy. Using lipoplex (Lipo-PEG-PEI-complex, LPPC) encapsulated doxorubicin (DOX) and carrying CpG oligodeoxynucleotide; the transdermally administered nano-liposomal drug complex (LPPC-DOX-CpG) would have high cytotoxicity and immunostimulatory activity to suppress systemic metastasis of melanoma. LPPC-DOX-CpG dramatically suppressed subcutaneous melanoma growth by inducing tumor cell apoptosis and recruiting immune cells into the tumor area. Animal studies further showed that the colonization and growth of spontaneously metastatic melanoma cells in the liver and lung were suppressed by transdermal LPPC-DOX-CpG. Furthermore, NGS analysis revealed IFN-γ and NF-κB pathways were triggered to recruit and activate the antigen-presenting-cells and effecter cells, which could activate the anti-tumor responses as the major mechanism responsible for the therapeutic effect of LPPC-DOX-CpG. Finally, we have successfully proved transdermal LPPC-DOX-CpG as a promising penetrative carrier to activate systemic anti-tumor immunity against subcutaneous and metastatic tumor.

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来源期刊
CiteScore
8.10
自引率
3.60%
发文量
104
审稿时长
4.6 months
期刊介绍: Nanomedicine: Nanotechnology, Biology and Medicine (NBM) is an international, peer-reviewed journal presenting novel, significant, and interdisciplinary theoretical and experimental results related to nanoscience and nanotechnology in the life and health sciences. Content includes basic, translational, and clinical research addressing diagnosis, treatment, monitoring, prediction, and prevention of diseases.
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