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

• 批准号: 10041396
• 负责人: WEI-HENG SHIH
• 金额: $ 7.11万
• 依托单位: DREXEL UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-07-01 至 2022-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10041396
• 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

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：生物组织成像是识别疾病的重要组成部分。在所有影像中 在多种方法中，将特定生物标志物与明亮的成像荧光团结合的免疫染色是最有效的 可靠的。近红外（NIR）发射材料将是理想的，因为它们可以避免干扰 组织自发荧光，水的吸光度极小。目前 FDA 唯一批准的近红外染料是 吲哚菁绿 (ICG) 荧光团已被广泛探索用于检测残留癌细胞 通过肿瘤的增强渗透性和保留（EPR）效应来实现手术伤口。然而ICG并不亮眼 在水中量子产率 (QY) 较低，约为 2%。最近，卤化物钙钛矿纳米晶（HPNC） 式 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 阴离子（如 Cl、Br 或 I）已被证明是一种出色的新型光致发光材料，具有高 QY接近100%。 我们建议使用 HPNC 作为明亮的荧光团来创建可以对组织进行成像的近红外分子探针 在单细胞水平上进行，无需显微放大。预计这样的活动会取得成功 研究将产生一种明亮的分子探针，可用于临床环境中的各种成像 应用程序。例如，它可用于确定手术是否已清除所有癌细胞 通过评估肿瘤边缘，从手术期间的患者身上获取。 面临的挑战是 NIR HPNC 在环境条件下不稳定，必须受到保护 湿气，更不用说浸入水中进行生物应用了。最近的研究表明，二氧化硅涂层 卤化铯铅颗粒稳定，可通过内化用于细胞成像。为了 生物成像、生物分子缀合过程需要稳定的水悬浮液。然而，到目前为止 目前还没有方法可以产生稳定的水性卤化物钙钛矿颗粒悬浮液。 在初步研究中，我们表明使用疏水性-亲水性嵌段共聚物，有可能 创建 MAPbBr3 的水悬浮液。然而，暂停只能持续 30 分钟， 由于对颗粒的水损害保护不足，后来沉降了。最近我们 首先使用二氧化硅前体来涂覆和保护 MAPbBr3 NC，然后添加亲水性 - 疏水-亲水三嵌段共聚物来分散颗粒，我们可以生产水悬浮液 MAPbBr3 稳定一个月。 该研究的目的是创建稳定的 MAPbI3 水性近红外 HPNC 悬浮液。在任务 1 中，我们 将首先使用二氧化硅涂覆 MAPbI3，然后添加三嵌段共聚物，最后添加 将溶剂从甲苯转移至水。在任务 2 中，我们将通过将抗体附着到 HPNC 并用它们对细胞进行染色。 >10 的良好信噪比表明染色合理。