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具有独特肿瘤靶向和酶诱导局部保留特性的功能性肽纳米纤维

Functional Peptide Nanofibers with Unique Tumor Targeting and Enzyme-Induced Local Retention Properties.

作者信息

Bellat Vanessa, Ting Richard, Southard Teresa L, Vahdat Linda, Molina Henrik, Fernandez Joseph, Aras Omer, Stokol Tracy, Law Benedict

机构信息

Molecular Imaging Innovations Institute, Department of Radiology, Weill Cornell Medicine, 413 East 69 Street, New York, NY 10021, USA,

Department of Biomedical Sciences, College of Veterinary Medicine, Cornell University, Upper Tower Road, Ithaca, New York, NY 14853, USA.

出版信息

Adv Funct Mater. 2018 Oct 31;28(44). doi: 10.1002/adfm.201803969. Epub 2018 Sep 14.

DOI:10.1002/adfm.201803969
PMID:30505260
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6261308/
Abstract

An effective tumoral delivery system should show minimal removal by the reticuloendothelial system (RES), promote tumor uptake and penetration, and minimize on-site clearance. This study reports the design and synthesis of advanced self-assembling peptide nanofiber precursor (NFP) analogues. The peptidic nature of NFP offers the design flexibility for on-demand customization with imaging agents and surface charges while maintaining a set size, allowing for real-time monitoring of kinetic and dynamic tumoral delivery by multimodal fluorescence/positron emission tomography/computed tomography (fluo/PET/CT) imaging, for formulation optimization. The optimized glutathione (GSH)-NFP displays a reduced capture by the RES as well as excellent tumor targeting and tissue invasion properties compared to naive NFP. Inside a tumor, GSH-NFP can structurally transform into ten times larger interfibril networks, serving as in situ depot that promotes weeks-long local retention. This nanofiber, which can further be designed to release the active pharmacophores within a tumor microenvironment, displays a superior therapeutic efficacy for inhibiting disease progression and improving the survival of animals bearing triple-negative breast cancer tumors compared to free drug and liposome formulation of the drug, in addition to a favorable toxicity profile.

摘要

一种有效的肿瘤递送系统应表现出最小程度地被网状内皮系统（RES）清除，促进肿瘤摄取和渗透，并将局部清除降至最低。本研究报告了先进的自组装肽纳米纤维前体（NFP）类似物的设计与合成。NFP的肽性质为与成像剂和表面电荷进行按需定制提供了设计灵活性，同时保持设定的尺寸，从而能够通过多模态荧光/正电子发射断层扫描/计算机断层扫描（fluo/PET/CT）成像对肿瘤递送的动力学和动态过程进行实时监测，以优化制剂。与天然NFP相比，优化后的谷胱甘肽（GSH）-NFP显示出被RES捕获的减少以及优异的肿瘤靶向和组织侵袭特性。在肿瘤内部，GSH-NFP可在结构上转变为比其大十倍的纤维间网络，作为原位储库促进长达数周的局部滞留。这种纳米纤维可进一步设计为在肿瘤微环境中释放活性药效基团，与游离药物和药物脂质体制剂相比，在抑制疾病进展和提高三阴性乳腺癌荷瘤动物存活率方面显示出卓越的治疗效果，且具有良好的毒性特征。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/83ec/6261308/2e7273dbfe67/nihms-989934-f0008.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/83ec/6261308/2e7273dbfe67/nihms-989934-f0008.jpg

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