权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

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.

项目简介：生物组织成像是识别疾病的重要组成部分。在所有的图像中方法：将特定的生物标志物与明亮的成像荧光团相结合进行免疫染色是最常用的方法。可靠。近红外(NIR)发射材料将是理想的，因为它们可以避免组织自发荧光，对水有最小的吸光度。目前FDA批准的唯一近红外染料是吲哚青绿(ICG)荧光团已被广泛探索用于检测手术创伤通过肿瘤的增强型渗透性和滞留(EPR)效应。然而，ICG并不聪明在水中的低量子产率(QY)约为2%。最近卤化物钙钛矿纳米晶(HPNC) 式ABX3(式中，A=有机氨阳离子或Cs，B=金属阳离子，如铅或锡，X=卤化物阴离子，如氯、溴或碘)已被证明是一种出色的新型光致发光材料，具有很高的 QY接近100%。我们建议使用HPNC作为一种明亮的荧光团来制造可以对组织成像的近红外分子探针在单细胞水平上，不需要显微扩增。预计这样一个项目的成功研究将导致一种明亮的分子探针，可以用于临床环境中的各种成像申请。例如，它可以用来确定手术是否移除了所有的癌细胞在手术过程中通过评估肿瘤边缘从患者那里获得。挑战在于，近红外HPNC在环境条件下不稳定，必须受到保护湿气，更不用说浸入用于生物应用的水中了。最近有研究表明，二氧化硅涂层铯的卤化铅颗粒是稳定的，通过内化可以用于成像细胞。为生物分子的偶联过程需要稳定的水相悬浮液进行生物成像。然而，到目前为止，目前还没有产生稳定的卤化物钙钛矿水悬浮液的方法。在初步研究中，我们表明使用疏水-亲水嵌段共聚物是可能的以产生MAPbBr3的水悬浮液。然而，停职只有30分钟，而且由于对颗粒的水损害保护不足，后来解决了问题。最近，我们使用二氧化硅前驱体包覆和保护MAPbBr3 NCS，然后添加亲水性- 疏水-亲水三嵌段共聚物分散粒子，可制成水悬浮液可以稳定一个月的MAPbBr3。本研究的目的是为MAPbI3创造稳定的近红外HPNC水悬浮液。在任务1中，我们将首先使用二氧化硅包覆MAPbI3，然后添加三嵌段共聚物，然后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加到 HPNC，并用它们来染色细胞。良好的信噪比&gt；10表示染色合理。