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.

项目摘要：成像生物组织是鉴定疾病的重要组成部分。在所有成像中方法，特定生物标志物与明亮成像荧光团结合的免疫染色是最多的可靠的。近红外（NIR）发射材料将是理想的选择，因为它们可以避免干扰组织自动荧光，水吸光度最低。目前，FDA唯一经批准的NIR染料是氨基苯胺绿色（ICG）荧光团已进行了广泛的探索以检测到残留的癌细胞通过肿瘤增强的渗透性和保留率（EPR）效应的手术伤口。但是，ICG并不明亮在水中的低量子产率（QY）约为2％。最近的卤化物钙钛矿纳米晶体（HPNC）配方ABX3（其中A =有机铵阳离子或CS，B =金属阳离子，例如Pb或Sn，X =卤化物 Cl，Br或I）等阴离子已被证明是一种出色的新光致发光材料，高 QY近100％。我们建议将HPNC用作明亮的荧光团来创建NIR分子探针，以形象组织在单细胞水平上无需显微放大。预计这样的成功研究将导致明亮的分子探针，可用于各种成像的临床环境申请。例如，它可用于确定手术是否已清除了所有癌细胞通过评估肿瘤边缘在手术过程中的患者。挑战是NIR HPNC在环境条件下不稳定，必须受到保护水分，更不用说浸入水中以进行生物学应用了。最近显示了二氧化硅涂层铯铅卤化物颗粒稳定，可用于通过内在化来成像细胞。为了生物分子共轭过程需要生物成像，稳定的水性悬浮液。但是，到目前为止没有方法可以生成稳定的卤化物钙钛矿颗粒悬浮液。在初步研究中，我们表明使用疏水 - 综合性块聚合物，这是可能的创建Mapbbr3的水性悬浮液。但是，悬浮液可能仅存在30分钟，并且此后由于对颗粒的水损害的保护不足而定为解决。最近我们使用二氧化硅前体涂层和保护Mapbbr3 NCS，然后添加亲水性 - 疏水 - 综合三嵌段共聚物分散颗粒，我们可以产生水性悬浮液稳定一个月的mapbbr3。该研究的目的是创建MAPBI3的NIR HPNC悬浮液。在任务1中，我们将使用二氧化硅首先覆盖Mapbi3，然后添加三嵌段共聚物，然后再添加将溶剂从甲苯转移到水。在任务2中，我们将通过将抗体附加到 HPNC并用它们对细胞染色。 > 10的良好信噪比将表明合理的染色。