A nanoparticle size series for in vivo fluorescence imaging.
A nanoparticle size series for in vivo fluorescence imaging.
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DOI：
10.1002/anie.201003142
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发表时间：
2010-11-08
影响因子：
16.6
通讯作者：
Bawendi, Moungi G.
中科院分区：
文献类型：
--
作者：
Popovic, Zoran;Liu, Wenhao;Chauhan, Vikash P.;Lee, Jungmin;Wong, Cliff;Greytak, Andrew B.;Insin, Numpon;Nocera, Daniel G.;Fukumura, Dai;Jain, Rakesh K.;Bawendi, Moungi G.
用于癌症治疗或成像的纳米颗粒载体的任何设计都必须考虑纳米颗粒与肿瘤微环境的相互作用。尺寸、电荷和形状已被证明主导这种相互作用。[1，2]由于可用纳米尺寸探针的限制，同时用不同尺寸的颗粒体内探测实体肿瘤迄今为止一直具有挑战性。[3-5]荧光葡聚糖和其他大分子探针已被用于活体显微镜的研究，但样本的异质性阻止了它们用于同一肿瘤内一系列大小的探针的同时成像。[5]MRI造影剂是另一组有吸引力的探针，因为该技术具有微创性[6，7]，但MRI的较低空间分辨率限制了肿瘤内异质性的成像，并且该技术不允许同时成像和跟踪同一肿瘤内的一系列尺寸的探针。除了独特的和狭窄的流体动力学尺寸，用于空间和时间跟踪分布的纳米粒子探针必须满足以下成功的体内研究的最低标准：胶体稳定性，低蛋白吸附，和高信号背景水平。本文提出的工作旨在创建一个纳米颗粒工具集，该工具集能够同时在同一实体瘤内对不同尺寸的纳米颗粒的分布进行体内研究。我们专注于在一个狭窄的电荷范围内的荧光颗粒和恒定的形状在10-150 nm的尺寸范围内。静脉注射后该尺寸范围内的纳米颗粒的行为特别令人感兴趣，因为它涵盖了临床批准的用于癌症治疗的基于纳米颗粒的药物制剂的尺寸范围。[8]量子点（QD）由于其在可见光和红外区域的光谱可调谐性，是用于生物成像的特别有吸引力的荧光材料。[9，10]量子点可以在很宽的波长范围内被激发，具有高的双光子吸收截面，并且相对光稳定，因此允许长时间的观察。取决于有机封端配体，水分散性单QD的流体动力学直径（HD）可以在5- 40 nm的范围内。[11更大尺寸的纳米颗粒结构（> 40 nm）以前已经通过聚集，[13，14]通过将QD吸附到更大的颗粒上，[15]或通过在单个QD周围生长二氧化硅壳来实现。[16]然而，这些较大的构建体倾向于在它们的尺寸范围、它们在水溶液中的稳定性或它们的亮度方面具有限制。在此，我们提出了尺寸范围为10-150 nm的纳米颗粒，其显示不同的发射波长，用于体内运输的同时成像，并且同时是高度发光的、非聚集的和生物相容的。对于小尺寸颗粒（ca. 10- 20 nm HD），我们使用最近开发的PIL涂层QD（图1a）。[17]PIL涂层量子点具有明确的HD，并且在水溶液中稳定且明亮（QY= 65%）。对于20-70 nm大小的颗粒，通过反相微乳液方法用二氧化硅层涂覆单个QD（CdSe/CdS，[17]核/壳，具有油胺和油酸帽）（图1b）。[16]通过改变二氧化硅源的量来控制二氧化硅壳的厚度。起始QD结构的选择被证明是至关重要的，以保持纳米粒子的光致发光效率后的二氧化硅层的生长。在CdSe/ZnS和CdSe/CdZnS颗粒的情况下，在二氧化硅壳的生长之后，QD荧光在很大程度上被猝灭。相反，成功的配方实现了CdSe/CdS纳米粒子（4 CdS…
Any design of nanoparticle vectors for cancer therapy or imaging must take into account the interaction of the nanoparticles with the tumor microenvironment. Size, charge, and shape have been shown to dominate this interaction.[1, 2] In vivo probing of solid tumors with particles of different sizes simultaneously has thus far been challenging due to the limitations of available nanosized probes.[3–5] Fluorescent dextrans and other macromolecule probes have been used in studies with intravital microscopy, but heterogeneities across samples has prevented their use for the simultaneous imaging of a size series of probes within the same tumor.[5] MRI contrast agents are another attractive set of probes due to the minimally invasive nature of the technology,[6, 7] but the lower spatial resolution of MRI limits the imaging of heterogeneity within tumors, and the technique does not allow simultaneous imaging and tracking of a size series of probes within the same tumor. Besides being of distinctive and narrow hydrodynamic sizes, nanoparticle probes used for spatial and temporal tracking of distributions must satisfy the following minimum criteria for successful in vivo studies: colloidal stability, low protein adsorption, and high signal-to-background levels. The work presented herein aims to create a nanoparticle toolset that enables the in vivo study of distributions of different size nanoparticles simultaneously within the same solid tumor. We focus on fluorescent particles within a narrow charge range and constant shape within the size range of 10–150 nm. The behavior of nanoparticles in this size range following intravenous injection is of particular interest because it encompasses the size range of clinically approved nanoparticlebased drug formulations for cancer therapy.[8] Quantum dots (QDs) are especially attractive fluorescent materials for biological imaging due to their spectral tunability in the visible and infrared regions.[9, 10] QDs can be excited over a wide range of wavelengths, have high two-photon absorption cross-section, and are relatively photo-stable, thus allowing long observation times. The hydrodynamic diameter (HD) of water-dispersible single QDs can range from 5–40nm depending on the organic capping ligands.[11, 12] Larger-sized nanoparticle constructs (> 40nm) have been previously achieved by aggregation,[13, 14] by adsorbing QDs to larger particles,[15] or by growing silica shells around individual QDs.[16] However, these larger constructs tend to have limitations either in their size range, their stability in aqueous solution, or in their brightness. Herein, we present nanoparticles in the size range of 10–150 nm that display distinct emission wavelengths for simultaneous imaging of transport in vivo and simultaneously are highly luminescent, non-aggregated, and biocompatible. For small-size particles (ca. 10–20nm HD), we used recently developed PIL-coated QDs (Figure1a).[17] PIL-coated QDs have a well-defined HD and they are stable and bright in aqueous solutions (QY= 65%). For 20–70 nmsized particles, individual QDs (CdSe/CdS,[17] core/shell, with oleylamine and oleic acid caps) were coated with a silica layer by a reverse microemulsion method (Figure 1b).[16] The thickness of the silica shell was controlled by varying the amount of the silica source. The choice of starting QD structure proved to be crucial for preserving the photoluminescence efficiency of the nanoparticles after the growth of the silica layer. In the case of CdSe/ZnS and CdSe/CdZnS particles, the QD fluorescence was largely quenched after the growth of the silica shell. Conversely, a successful formulation was achieved for CdSe/CdS nanoparticles (4 CdS …
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影响因子：
16.6
作者：
Zhuang, Jiaqi;Wu, Huimeng;Cao, Y. Charles
通讯作者：
Cao, Y. Charles
影响因子：
8.6
作者：
Koole, Rolf;van Schooneveld, Matti M.;Meijerink, Andries
通讯作者：
Meijerink, Andries
影响因子：
56.9
作者：
Bruchez, M;Moronne, M;Alivisatos, AP
通讯作者：
Alivisatos, AP
影响因子：
15
作者：
Liu, Wenhao;Choi, Hak Soo;Bawendi, Moungi
通讯作者：
Bawendi, Moungi
影响因子：
4.9
作者：
Meng, FH;Engbers, GHM;Feijen, J
通讯作者：
Feijen, J