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InP/ZnS Luminescent Quantum Dots for Bioimaging with Improved Cellular Targeting Capabilities

用于生物成像的 InP/ZnS 发光量子点具有改进的细胞靶向能力

基本信息

批准号：
1904600
负责人：
Zeev Rosenzweig
金额：
$ 43万
依托单位：
University of Maryland Baltimore County
依托单位国家：
美国
项目类别：
Standard Grant
财政年份：
2019
资助国家：
美国
起止时间：
2019-08-01 至 2024-07-31
项目状态：
已结题

来源：
https://www.nsf.gov/awardsearch/showAward?AWD_ID=1904600&HistoricalAwards=false
关键词：
InP ZnS Luminescent Quantum Dots

项目摘要

Quantum dots are extremely small nanocrystals of semiconductors that are 100,000 times smaller than a grain of salt and contain just a few thousand atoms. When exposed to light, quantum dots luminesce, and the color of their emitted light depends on their size. It is these unique optical properties that make quantum dots useful in applications ranging from cell phones to light emitting diodes (LEDs). Quantum dots have also attracted the attention of the biotechnology community due to their potential use in bioimaging and biosensing applications. However, most quantum dots contain heavy metals like cadmium and lead that are toxic to living cells and their surfaces quickly become coated with proteins and lipids that degrade their stability. With support from the Macromolecular, Supramolecular and Nanochemistry Program in the Division of Chemistry, Professor Zeev Rosenzweig in the Department of Chemistry and Biochemistry at the University of Maryland Baltimore County (UMBC) is developing non-toxic quantum dots from indium phosphide. Working with his students and collaborator Dr. Karen Leinkamp at Albert-Ludwigs Universitat in Germany, Professor Rosenzweig is modifying the surface of the quantum dots with novel polymers that inhibit the formation of protein corona on their surface, allowing them to maintain their bright luminescence and stability in biological solutions. Their discoveries could have broad implications for using semiconductor quantum dots in biological applications. The project provides interdisciplinary research training opportunities for graduate and undergraduate students involved. Professor Rosenzweig and his team are also actively engaged in outreach to nearby high schools to introduce students to concepts in nanoscience and nanotechnology, including their impact on human health and the environment.Highly emitting quantum dots (QDs) are currently limited in their chemical stability in complex biological media, and in their cellular targeting efficiency due to protein corona formation. The project is addressing these limitations, enabling the use of InPZn/ZnS QDs as non-toxic bioimaging probes. The goals of the project are realized through the following specific aims: Aim 1) Modifying the surface of InPZn/ZnS QD with oxonorbornene-based polymers that allow systematic functionalization of the polymer side chains to inhibit corona formation. Aim 2) Development and use of a high-resolution fluorescence microscopy system, typically used in single molecule fluorescence studies, to follow in real time the process of protein corona formation on InPZn/ZnS QDs without photodegradation, or the need for large quantities of nanoparticles. Aim 3) Demonstrate that the surface modification of InPZn/ZnS QDs with oxonorbornene polymers results in protein corona formation inhibition, and increased macrophage targeting efficiency. The project provides interdisciplinary research training opportunities for graduate and undergraduate students. It also enhances the recruitment of students from underrepresented groups to scientific research in nanomaterials chemistry through partnership with the national Interdisciplinary Consortium for Research and Educational Access in Science and Engineering (INCREASE).This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

量子点是极小的半导体纳米晶体，比一粒盐粒小10万倍，只包含几千个原子。当暴露于光时，量子点发光，其发射光的颜色取决于它们的大小。正是这些独特的光学性质使量子点在从手机到发光二极管（LED）的应用中非常有用。量子点由于其在生物成像和生物传感应用中的潜在用途也吸引了生物技术界的注意。然而，大多数量子点含有重金属，如镉和铅，对活细胞有毒，它们的表面很快就会被蛋白质和脂质所覆盖，从而降低它们的稳定性。在化学系大分子、超分子和纳米化学项目的支持下，马里兰州巴尔的摩县大学（UMBC）化学和生物化学系的Zeev Rosenzweig教授正在从磷化铟中开发无毒量子点。Rosenzweig教授与他的学生和合作者Karen Leinkamp博士在德国的Albert-Ludwigs大学合作，用新型聚合物修饰量子点的表面，抑制其表面蛋白质冠的形成，使它们能够在生物溶液中保持明亮的发光和稳定性。他们的发现可能对半导体量子点在生物应用中的应用产生广泛的影响。该项目为研究生和本科生提供跨学科的研究培训机会。Rosenzweig教授和他的团队还积极参与到附近高中的外展活动中，向学生介绍纳米科学和纳米技术的概念，包括它们对人类健康和环境的影响。目前，高发射量子点（QD）在复杂生物介质中的化学稳定性有限，并且由于蛋白质冠的形成，其细胞靶向效率有限。该项目正在解决这些限制，使InPZn/ZnS量子点作为无毒生物成像探针的使用成为可能。该项目的目标是通过以下具体目标实现的：目标1）用氧代降冰片烯基聚合物修饰InPZn/ZnS QD的表面，使聚合物侧链系统官能化以抑制电晕形成。目的2）开发和使用通常用于单分子荧光研究的高分辨率荧光显微镜系统，以真实的时间跟踪蛋白质在InPZn/ZnS量子点上形成冠的过程，而不需要光降解或大量的纳米颗粒。目的3）证明用氧代降冰片烯聚合物对InPZn/ZnS量子点进行表面修饰可以抑制蛋白质冠状结构的形成，并提高巨噬细胞靶向效率。该项目为研究生和本科生提供跨学科的研究培训机会。它还通过与国家科学和工程研究和教育机会跨学科联盟（INCREASE）的合作关系，加强了从代表性不足的群体中招募学生进行纳米材料化学科学研究的工作。该奖项反映了NSF的法定使命，并通过使用基金会的智力价值和更广泛的影响审查标准进行评估，被认为值得支持。