Engineered magnetic hybrid nanoparticles with enhanced relaxivity for tumor imaging
Engineered magnetic hybrid nanoparticles with enhanced relaxivity for tumor imaging
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DOI：
10.1016/j.biomaterials.2013.07.003
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发表时间：
2013-10-01
期刊：
影响因子：
14
通讯作者：
Decuzzi, Paolo
中科院分区：
文献类型：
--
作者：
Aryal, Santosh;Key, Jaehong;Decuzzi, Paolo
临床使用的磁共振成像造影剂存在缺乏特异性、循环时间短、弛豫不充分等问题。本文介绍了一种一步法合成磁性脂质-聚合物(杂化)纳米颗粒(MHNPs)的方法，该纳米颗粒包裹着5 nm的超顺磁性氧化铁颗粒(USPIO)，并用Gd3+离子进行修饰。MHNPs由疏水的聚(乳酸-乙醇酸)(PLGA)核组成，含有高达5%的USPIO(w/w)，由脂质和聚乙二醇(PEG)稳定。Gd3+离子直接与外膜脂单分子层结合。提出了三种不同的纳米粒子构型，包括仅Gd-MHNPs(Gd-MHNPs)、仅USPIO(Fe-MHNPs)及其组合(MHNPs)。这三种MHNPs的流体力学直径都在150 nm左右。Gd-MHNPs的纵向弛豫系数r(1)=12.95+/-0.53(Mm S)(-1)，约为传统Gd基对比剂的4倍(r(1)=3.4(Mm S)(-1))；MHNPs的横向弛豫率r(2)=164.07+/-7.0(Mm S)(-1)，比大多数传统体系(r(2)类似于50(Mm S)(-1)大3~4倍)。在荷黑色素瘤的小鼠中，Gd的元素分析显示，在注射后24小时，大约3%的MHNPs累积在肿瘤中，2%的MHNPs仍在血液中循环。在临床3T核磁共振扫描仪中，MHNPs提供了显著的对比，证实了观察到的肿瘤沉积。这种方法还可以在MHNP核心中共负载疏水治疗化合物，为治疗系统铺平道路。(C)2013爱思唯尔有限公司。保留所有权利。
Clinically used contrast agents for magnetic resonance imaging (MRI) suffer by the lack of specificity; short circulation time; and insufficient relaxivity. Here, a one-step combinatorial approach is described for the synthesis of magnetic lipid-polymer (hybrid) nanoparticles (MHNPs) encapsulating 5 nm ultrasmall super-paramagnetic iron oxide particles (USPIOs) and decorated with Gd3+ ions. The MHNPs comprise a hydrophobic poly(lactic acid-co-glycolic acid) (PLGA) core, containing up to similar to 5% USPIOs (w/w), stabilized by lipid and polyethylene glycol (PEG). Gd3+ ions are directly chelated to the external lipid monolayer. Three different nanoparticle configurations are presented including Gd3+ chelates only (Gd-MHNPs); USPIOs only (Fe-MHNPs); and the combination thereof (MHNPs). All three MHNPs exhibit a hydrodynamic diameter of about 150 nm. The Gd-MHNPs present a longitudinal relaxivity (r(1) = 12.95 +/- 0.53 (mM s)(-1) about four times larger than conventional Gd-based contrast agents (r(1) = 3.4 (mM s)(-1)); MHNPs have a transversal relaxivity of r(2) = 164.07 +/- 7.0 (mM s)(-1), which is three to four times larger than most conventional systems (r(2) similar to 50 (mM s)(-1)). In melanoma bearing mice, elemental analysis for Gd shows about 3% of the injected MHNPs accumulating in the tumor and 2% still circulating in the blood, at 24 h post-injection. In a clinical 3T MRI scanner, MHNPs provide significant contrast confirming the observed tumor deposition. This approach can also accommodate the co-loading of hydrophobic therapeutic compounds in the MHNP core, paving the way for theranostic systems. (C) 2013 Elsevier Ltd. All rights reserved.