ɑvβ3-targeted liposomal drug delivery system with attenuated immunogenicity enabled by linear pentapeptide for glioma therapy.,Journal of Controlled Release

当前位置： X-MOL 学术 › J. Control. Release › 论文详情

Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)

ɑvβ3-targeted liposomal drug delivery system with attenuated immunogenicity enabled by linear pentapeptide for glioma therapy.
Journal of Controlled Release ( IF 10.5 ) Pub Date : 2020-04-08 , DOI: 10.1016/j.jconrel.2020.04.009
Jinyang Li ₁ , Zhilan Chai ₁ , Jiasheng Lu ₁ , Cao Xie ₁ , Danni Ran ₁ , Songli Wang ₁ , Jianfen Zhou ₁ , Weiyue Lu ₂

Affiliation

Owing to the binding capacity to ɑvβ3 integrin overexpressed on glioma, vasculogenic mimicry and neovasculature, the peptide c(RGDyK) has been exploited pervasively to functionalize nanocarriers for targeted delivery of bioactives. The former study in our group substantiated the immunotoxicity of c(RGDyK)-modified liposome, and this unfavorable immunogenicity is known to compromise blood circulation, targeting efficacy and therapeutic outcome. Therefore, we need to find a superior alternative ligand in order to evade the exquisite immuno-sensitization. We developed mn by structure-guided peptide design and retro-inverso isomerization technique, which was experimentally substantiated to have exceptional binding affinity to ɑvβ3 integrin. Besides mn does not have affinity toward normal liver cells and kidney cells, which c(RGDyK) possesses in a certain degree. Warranting that mn and c(RGDyK) anchored ɑvβ3, we formulated peptide-tethered liposomes and investigated in vivo bio-fate. Compared with c(RGDyK)-modified liposome, mn-modified liposome presented longer blood circulation and reduced ingestion by Kupffer cells with decreased retention in liver accordingly, benefitting from attenuated anti-liposome IgG and IgM response elicited by multiple sequential doses. Those merits strengthened the anti-glioma efficacy of ɑvβ3-targeted doxorubicin-loaded liposomes, proving the importance of immunocompatibility in process of targeted drug delivery.

中文翻译：

线性五肽使vβ3靶向脂质体药物递送系统的免疫原性降低，可用于神经胶质瘤治疗。

由于与在神经胶质瘤，血管生成模拟物和新脉管系统中过表达的ɑvβ3整联蛋白的结合能力，肽c（RGDyK）已被广泛用于功能化纳米载体以靶向递送生物活性物质。我们小组中的前一项研究证实了c（RGDyK）修饰的脂质体的免疫毒性，并且已知这种不利的免疫原性会损害血液循环，靶向疗效和治疗结果。因此，我们需要寻找一种更好的替代配体来逃避精致的免疫敏化。我们通过结构引导的肽设计和逆反异构化技术开发了mn，经实验证实，其与ɑvβ3整联蛋白具有出色的结合亲和力。mn对正常的肝细胞和肾细胞没有亲和力，c（RGDyK）在某种程度上拥有什么。为保证mn和c（RGDyK）锚定ɑvβ3，我们配制了肽链脂质体并研究了体内生物命运。与c（RGDyK）修饰的脂质体相比，mn修饰的脂质体呈现更长的血液循环并减少了Kupffer细胞的摄取，从而减少了在肝脏中的滞留，这得益于多次连续剂量引起的抗脂质体IgG和IgM应答减弱。这些优点增强了靶向ɑvβ3的阿霉素脂质体的抗神经胶质瘤功效，证明了免疫相容性在靶向药物递送过程中的重要性。mn修饰的脂质体表现出更长的血液循环并被Kupffer细胞摄取减少，因此在肝脏中的保留减少，这得益于多次连续剂量引起的抗脂质体IgG和IgM应答减弱。这些优点增强了靶向ɑvβ3的阿霉素脂质体的抗神经胶质瘤功效，证明了免疫相容性在靶向药物递送过程中的重要性。mn修饰的脂质体表现出更长的血液循环并被Kupffer细胞摄取减少，因此在肝脏中的保留减少，这得益于多次连续剂量引起的抗脂质体IgG和IgM应答减弱。这些优点增强了靶向ɑvβ3的阿霉素脂质体的抗神经胶质瘤功效，证明了免疫相容性在靶向药物递送过程中的重要性。

更新日期：2020-04-08

点击分享查看原文

点击收藏

阅读更多本刊最新论文本刊介绍/投稿指南11