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

量子点是非常小的半导体纳米晶体，比一粒盐小10万倍，只包含几千个原子。当暴露在光线下时，量子点会发光，它们发出的光的颜色取决于它们的大小。正是这些独特的光学特性使得量子点在从手机到发光二极管（led）的各种应用中都很有用。量子点由于其在生物成像和生物传感方面的潜在应用，也引起了生物技术界的关注。然而，大多数量子点含有镉和铅等重金属，这些重金属对活细胞有毒，它们的表面很快就会被蛋白质和脂质覆盖，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，马里兰大学巴尔的摩县分校（UMBC）化学和生物化学系的Zeev Rosenzweig教授正在用磷化铟开发无毒量子点。罗森茨威格教授与他的学生和合作者、德国阿尔伯特-路德维希斯大学的凯伦·莱坎普博士合作，正在用新型聚合物修饰量子点的表面，这种聚合物可以抑制表面蛋白质电晕的形成，使它们在生物溶液中保持明亮的发光和稳定性。他们的发现可能对在生物应用中使用半导体量子点具有广泛的意义。该项目为参与的研究生和本科生提供跨学科的研究训练机会。罗森茨威格教授和他的团队还积极与附近的高中接触，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（QDs）在复杂生物介质中的化学稳定性以及由于蛋白质电晕形成而导致的细胞靶向效率受到限制。该项目正在解决这些限制，使使用InPZn/ZnS量子点作为无毒生物成像探针成为可能。该项目的目标是通过以下具体目标来实现的：目标1)用基于氧羰基的聚合物修饰InPZn/ZnS QD的表面，使聚合物侧链系统功能化以抑制电晕的形成。目标2)开发和使用高分辨率荧光显微镜系统，通常用于单分子荧光研究，实时跟踪InPZn/ZnS量子点上蛋白质电晕形成的过程，而不需要光降解，也不需要大量的纳米颗粒。目的3)证明oxonororbornene聚合物修饰InPZn/ZnS量子点表面可抑制蛋白冠形成，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训练机会。它还通过与国家科学与工程研究和教育机会跨学科联盟（INCREASE）的伙伴关系，加强从代表性不足的群体中招收学生从事纳米材料化学的科学研究。该奖项反映了美国国家科学基金会的法定使命，并通过使用基金会的知识价值和更广泛的影响审查标准进行评估，被认为值得支持。

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.