氯膦酸鹽脂質(zhì)體Clodronate Liposomes清除巨噬細(xì)胞全動物X射線監(jiān)測熒光納米顆粒

中文摘要：

納米顆粒 （NPs） 目前被開發(fā)用于藥物遞送和分子成像。然而，它們經(jīng)常在到達(dá)目標(biāo)之前被攔截，導(dǎo)致瞄準(zhǔn)效率和信噪比低下。它們往往會積聚在肺、肝、腎和脾臟等器官中。補(bǔ)救措施是迭代設(shè)計(jì) NP 表面特性和給藥策略，目前是一個耗時的過程，包括在不同時間點(diǎn)進(jìn)行器官解剖。為了改善這一點(diǎn)，我們提出了一種快速迭代方法，使用全動物X射線熒光（XRF）成像來系統(tǒng)地評估體內(nèi)NP分布。我們將這種方法應(yīng)用于鉬基NPs和氯膦酸鹽脂質(zhì)體（Clodronate Liposomes），用于腫瘤靶向與瞬時巨噬細(xì)胞耗竭，從而減少肺和肝臟中的積累并最終檢測腫瘤。XRF 計(jì)算機(jī)斷層掃描 （XFCT） 提供了腫瘤內(nèi) NP 分布的 3D 洞察。我們使用多尺度成像方法驗(yàn)證了結(jié)果，該方法具有染料摻雜的NPs和用于納米毒理學(xué)分析的基因表達(dá)分析。XRF成像在推進(jìn)臨床前藥代動力學(xué)研究中的治療和診斷方面具有潛力。

Abstract

Nanoparticles (NPs) are currently developed for drug delivery and molecular imaging. However, they often get intercepted before reaching their target, leading to low targeting efficacy and signal-to-noise ratio. They tend to accumulate in organs like lungs, liver, kidneys, and spleen. The remedy is to iteratively engineer NP surface properties and administration strategies, presently a time-consuming process that includes organ dissection at different time points. To improve this, we propose a rapid iterative approach using whole-animal x-ray fluorescence (XRF) imaging to systematically evaluate NP distribution in vivo. We applied this method to molybdenum-based NPs and clodronate liposomes（Liposoma） for tumor targeting with transient macrophage depletion, leading to reduced accumulations in lungs and liver and eventual tumor detection. XRF computed tomography (XFCT) provided 3D insight into NP distribution within the tumor. We validated the results using a multiscale imaging approach with dye-doped NPs and gene expression analysis for nanotoxicological profiling. XRF imaging holds potential for advancing therapeutics and diagnostics in preclinical pharmacokinetic studies.

論文題目：Iterative nanoparticle bioengineering enabled by x-ray fluorescence imaging

期刊名稱：SCIENCE ADVANCES

期卷日期：22 Mar 2024, Vol 10, Issue 12

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