中文摘要：

目前納米顆粒（NPs）已被研發(fā)應(yīng)用于藥物遞送與分子成像領(lǐng)域。然而，納米顆粒往往在抵達(dá)靶標(biāo)前就被機(jī)體截留，導(dǎo)致靶向效率和信噪比偏低，且易在肺、肝臟、腎臟、脾臟等器官中蓄積。

目前的解決辦法是反復(fù)優(yōu)化納米顆粒的表面特性與給藥策略，但該流程耗時(shí)冗長(zhǎng)，還需要在不同時(shí)間點(diǎn)進(jìn)行臟器解剖。為解決這一痛點(diǎn)，本研究提出一種快速迭代研究方案：利用活體動(dòng)物 X 射線熒光（XRF）成像，系統(tǒng)性評(píng)估納米顆粒的體內(nèi)分布。

我們將該方法應(yīng)用于鉬基納米顆粒與荷蘭Liposoma氯膦酸鹽脂質(zhì)體，通過(guò)瞬時(shí)耗竭巨噬細(xì)胞實(shí)現(xiàn)腫瘤靶向，有效減少了納米顆粒在肺部和肝臟的蓄積，最終實(shí)現(xiàn)腫瘤病灶檢出。X 射線熒光計(jì)算機(jī)斷層掃描（XFCT）可提供納米顆粒在腫瘤內(nèi)部分布的三維空間信息。

研究通過(guò)多尺度成像技術(shù)（摻雜熒光染料納米顆粒）及基因表達(dá)分析開(kāi)展納米毒理學(xué)特征研究，對(duì)上述結(jié)果進(jìn)行了驗(yàn)證。XRF 成像技術(shù)有望推動(dòng)臨床前藥代動(dòng)力學(xué)研究中治療與診斷手段的發(fā)展。

英文摘要：

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 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.

論文信息：

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

期刊名稱：Science Advances

時(shí)間期卷：Vol 10, Issue 12(2024)

在線時(shí)間：2024年3月22日

DOI: 10.1126/sciadv.adl2267

產(chǎn)品信息：

貨號(hào)：CP-005-005

規(guī)格：5ml+5ml

品牌：Liposoma

產(chǎn)地：荷蘭

名稱：Clodronate Liposomes&Control Liposomes

辦事處：靶點(diǎn)科技

Clodronate Liposomes氯膦酸鹽脂質(zhì)體在腫瘤模型種清除肝臟和脾臟巨噬細(xì)胞，實(shí)現(xiàn)納米顆粒（NPs）靶向腫瘤細(xì)胞遞送。荷蘭Liposoma巨噬細(xì)胞清除劑ClodronateLiposomes見(jiàn)刊于Science Advances：基于 X 射線熒光成像的納米顆粒迭代生物工程改造。

Liposoma巨噬細(xì)胞清除劑Clodronate Liposomes氯膦酸二鈉脂質(zhì)體清除巨噬細(xì)胞的材料和方法：

Ammonium heptamolybdate [AHM; (NH4)6Mo7O24·4H2O], PVP (55 kDa), Cy5.5 mono NHS ester (Cy5.5-NHS), (3-aminopropyl) triethoxysilane (APTES; C9H23NO3Si, 99%),  (TEA; C6H15N, ≥99%), dimethyl sulfoxide (DMSO; C2H6OS·H2O, ≥99%), tetraethyl orthosilicate (TEOS; C8H20O4Si ≥ 99%), and EA (C2H7NO, ≥99%) were all purchased from Sigma-Aldrich (Stockholm, Sweden). Ethanol (EtOH) absolute (≥99.8%) was obtained from VWR (Stockholm, Sweden). A MilliQ reference water purification system (Merck Millipore) was used for deionized (DI) water. Clodronate-encapsulated liposomes and empty (control) liposomes were purchased from Liposoma BV (Amsterdam, The Netherlands).

巨噬細(xì)胞清除材料和方法文獻(xiàn)截圖：