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Development of aqueous suspensions of organohalide perovskite nanocrystals for bioimaging

用于生物成像的有机卤化物钙钛矿纳米晶体水悬浮液的开发

基本信息

批准号：
10178015
负责人：
WEI-HENG SHIH
金额：
$ 7.12万
依托单位：
DREXEL UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2020
资助国家：
美国
起止时间：
2020-07-01 至 2024-04-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10178015
关键词：
Amines Ammonium Anions Antibodies Biological Carbodiimides Carbon Cations Cell Line Cells Cesium Clinical Development Disease Dyes Excision FDA approved Goals Hybrids Hydrophobicity Image Indocyanine Green Iodides Label Lead Light Link Malignant Neoplasms Metals Methods Microscopic Molecular Probes Near-infrared optical imaging Noise Operating Rooms Operative Surgical Procedures Particulate Patients Permeability Problem Solving Process Propylene Glycols Reaction Research Residual Cancers Resistance Resolution Series Signal Transduction Silicon Dioxide Solvents Spottings Stains Surgeon Surgical margins Surgical wound Suspensions Time Tissue imaging Tissues Toluene Visualization Water aqueous bioimaging cancer cell cellular imaging copolymer ethylene glycol fluorophore hydrophilicity imaging modality imaging probe improved innovation malignant breast neoplasm monomethylammonium ion nanocrystal nanoparticle near infrared dye particle perovskite quantum specific biomarkers success tumor

项目摘要

Project summary: Imaging biological tissues is an important part of identifying disease. Among all the imaging methods, immunostaining in which a specific biomarker is combined with a bright imaging fluorophore is most reliable. Near-infrared (NIR) emitting materials would be ideal because they can avoid the interference of tissue autofluorescence and have minimal absorbance by water. Currently the only FDA approved NIR dye is indocyanine green (ICG) fluorophore which has been explored extensively to detect residual cancer cells in the surgical wound through tumors' enhanced permeability and retention (EPR) effect. However, ICG is not bright with a low quantum yield (QY) of about 2% in water. Recently halide perovskites nanocrystals (HPNC) of formula ABX3 (where A=organic ammonium cation or Cs, B=metal cation such as Pb or Sn, and X=halide anion such as Cl, Br, or I) have been shown to be an outstanding new photoluminescent material with a high QY of nearly 100%. We propose to use HPNC as a bright fluorophore to create NIR molecular probe that can image tissues at a single-cell level without the need of microscopic amplification. It is anticipated that the success of such a study will lead to a bright molecular probe that can be used in the clinical setting for a variety of imaging applications. For example, it can be used to determine whether a surgery has removed all the cancer cells from patients during surgery by assessing the tumor margins. The challenge is that the NIR HPNCs are unstable in ambient condition and have to be protected from moisture, let alone immersed in water for biological applications. Recently it was shown that silica-coated cesium lead halide particles are stable and can be used for imaging cells through internalization. For bioimaging, stable aqueous suspensions are needed for biomolecule conjugation process. However, so far there has been no method to generate stable aqueous halide perovskite particle suspensions. In preliminary studies, we showed that using a hydrophobic-hydrophilic block-copolymer, it is possible to create aqueous suspensions of MAPbBr3. However, the suspensions could exist for only 30 minutes and settled out afterward due to the insufficient protection from water damage to the particles. More recently we used silica precursor to coat and protect the MAPbBr3 NCs first followed by the addition of a hydrophilic- hydrophobic-hydrophilic triblock copolymer to disperse the particles, we could produce an aqueous suspension of MAPbBr3 that is stable for a month. The aim of the research is to create stable aqueous NIR HPNC suspensions of MAPbI3. In task 1, we will use silica to coat the MAPbI3 first followed by the addition of triblock copolymers and subsequently transferring the solvent from toluene to water. In task 2 we will verify the process by attaching antibodies to the HPNC and use them to stain cells. A good signal-to-noise ratio of >10 would indicate a reasonable staining.

项目概述：生物组织成像是识别疾病的重要组成部分。在所有的成像中，方法，免疫染色，其中一个特定的生物标志物是结合一个明亮的成像荧光团是最可靠近红外（NIR）发射材料将是理想的，因为它们可以避免红外线的干扰。组织自体荧光并且具有最小的被水吸收。目前，FDA批准的唯一NIR染料是吲哚菁绿色（ICG）荧光团，其已被广泛探索以检测肿瘤组织中的残留癌细胞。通过肿瘤的增强渗透性和保留（EPR）效应，不过，ICG并不光明在水中具有约2%的低量子产率（QY）。最近，式ABX 3（其中A=有机铵阳离子或Cs，B=金属阳离子如Pb或Sn，X=卤化物阴离子如Cl、Br或I）已被证明是一种杰出的新型光致发光材料，具有高的 QY接近100%。我们建议使用HPNC作为明亮的荧光团来创建可以成像组织的近红外分子探针在单细胞水平上，而不需要显微放大。预计这样的成功这项研究将产生一种明亮的分子探针，可用于临床各种成像应用.例如，它可以用来确定手术是否已经去除了所有的癌细胞通过评估肿瘤边缘来获取患者的信息。挑战在于NIR HPNC在环境条件下不稳定，并且必须受到保护，潮湿，更不用说浸入水中用于生物应用。最近研究表明，卤化铯铅颗粒是稳定的，并可用于通过内化对细胞进行成像。为生物成像、稳定的水性悬浮液是生物分子缀合过程所需要的。然而到目前为止还没有产生稳定的含水卤化物钙钛矿颗粒悬浮液的方法。在初步研究中，我们表明，使用疏水-亲水嵌段共聚物，以产生MAPbBr 3的水性悬浮液。然而，暂停只能持续30分钟，随后由于不足以防止水对颗粒的损害而沉降。最近我们首先使用二氧化硅前体涂覆并保护MAPbBr 3 NC，然后添加亲水性- 疏水-亲水三嵌段共聚物来分散颗粒，我们可以制备水性悬浮液 MAPbBr 3的浓度可以稳定一个月该研究的目的是产生MAPbI 3的稳定的水性NIR HPNC悬浮液。在任务1中，我们将首先使用二氧化硅涂覆MAPbI 3，然后添加三嵌段共聚物，将溶剂从甲苯转移到水中。在任务2中，我们将通过将抗体附着到 HPNC并用它们来染色细胞。>10的良好信噪比将指示合理的染色。