靶向和协同癌症治疗的生物启发低密度脂蛋白共递送系统

IF 4.7 4区 医学 Q1 BIOTECHNOLOGY & APPLIED MICROBIOLOGY Nanomedicine: Nanotechnology, Biology and Medicine Pub Date : 2023-02-01 DOI:10.1016/j.nano.2022.102641
Qiaoling Zhu MD , Yajie Wang MD , Ying Huang MD , Yixuan Zi MD , Simin Yan PhD , Xianbiao Shi PhD , Jun Cai MD , Haixia Zhang MD , Jianfeng Sang PhD , Wenli Zhang PhD , Weihong Ge MD
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引用次数: 1

摘要

上皮间质转化(Epithelial-mesenchymal transition, EMT)是肿瘤侵袭转移的罪魁祸首。蜗牛是诱导EMT的关键转录因子,在肿瘤进展中起重要作用,通过小干扰RNA (small interfering RNA, siRNA)敲低其表达可能抑制肿瘤转移。在此,我们开发了一种核壳生物激发低密度脂蛋白(bio-LDL),其中蜗牛sirna负载的磷酸钙纳米颗粒被包裹为核心,阿霉素被包裹在外层的磷脂中,这些磷脂被合成的apoB100肽修饰,靶向LDL受体丰富的肿瘤细胞。Bio-LDL表现出ph响应性释放、溶酶体逃逸能力、增强的细胞毒性和诱导凋亡。Bio-LDL能显著抑制snail的表达,调控emt相关蛋白,减少肿瘤在体外的迁移和侵袭。生物低密度脂蛋白在体内也显示出良好的肿瘤靶向性和协同抑制肿瘤生长和转移。因此,多功能生物低密度脂蛋白将成为一种有前途的共递送载体,并具有临床翻译的潜在价值。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

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Bioinspired low-density lipoprotein co-delivery system for targeting and synergistic cancer therapy

Epithelial-mesenchymal transition (EMT) is the culprit of tumor invasion and metastasis. As a critical transcription factor that induces EMT, snail is of great importance in tumor progression, and knocking down its expression by small interfering RNA (siRNA) may inhibit tumor metastasis. Herein, we developed a core-shelled bioinspired low-density lipoprotein (bio-LDL) in which snail siRNA-loaded calcium phosphate nanoparticles were wrapped as the core and doxorubicin was embedded in the outer phospholipids modified with a synthetic peptide of apoB100 targeting LDL receptor-abundant tumor cells. Bio-LDL exhibited pH-responsive release, lysosomal escape ability, enhanced cytotoxicity and apoptotic induction. Bio-LDL could significantly inhibit the expression of snail and regulate EMT-related proteins to reduce tumor migration and invasion in vitro. Bio-LDL also displayed favorable tumor targeting and synergistic inhibition of tumor growth and metastasis in vivo. Therefore, the multifunctional bio-LDL will be a promising co-delivery vector and holds potential value for clinical translation.

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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.
期刊最新文献
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