CAREER: Pathways to in situ Medication: Liposomal Encapsulation, Transport in Microchannels and Delivery via Liposomal Membrane Crumpling

摘要：肿瘤等肿瘤疾病的主要治疗方法是对健康器官造成损害的放疗或毁容的手术。而在化疗中，只有一小部分给药剂量到达部位，而其余的则分布在全身，这限制了剂量并阻止了该方法实现其治疗功能。拟议研究的目标是开发和研究一种系统，通过这种系统，细胞样物体（脂质体）充满药物，在微通道中运输，并通过温度诱导，将有效载荷输送到精确的位置。该项目涉及固体力学、流体力学和材料科学相结合的生物材料行为研究的前沿实验和理论工作。这将是与雅培实验室医院产品部诊断小组的合作努力。这个问题将需要在机械科学中创造新的方向来处理脂质体的各种变形情况：不稳定引起的大管变形产生小的球形囊泡。在载药脂质体运输过程中，流体引起的变形和在药物递送过程中，温度引起的变形。这些思想在于弹性力学与流体力学的耦合。实验上，我们将使用荧光显微镜来监测脂质体的局部状态，我们将使用纳米压痕来探测脂质体的机械特性。微纤化技术将用于研究这些物体在微通道中的传输。该研究项目将与伊利诺伊大学厄巴纳-香槟分校正在开发的课程相结合，例如新开发的生物工程研究生课程和由PI在力学系新引入的生物力学的第二选择。本课程的主要兴趣是研究细胞和组织力学，生物学家接触到工程方法，工科学生接触到细胞生物学的协议。

Abstract:The main treatments of tumoral diseases such as cancer are radiation, which can be damaging to healthy organs or surgery, which can be disfiguring. While with chemotherapy only a small fraction of the administered dose reaches the site whilst the rest is distributed throughout the body which limits the dosage and prevents the method from achieving its function of curing. The objective of the proposed research is to develop and study a system whereby cell-like objects (liposomes) are filled with a drug, transported in microchannels and are induced, by temperature, to deliver the payload at precise locations. The project involves experimental and theoretical work at the forefront of research on the behavior of biological materials where solid mechanics, fluid mechanics and material sciences meet. This will be a cooperative effort with the diagnostic group of the Hospital Products Division at Abbott Laboratories.This problem will necessitate the creation of new directions in mechanical sciences to treat various cases of deformation of liposomes: Instability-induced deformation of large tubes to create small spherical vesicles. Flow induced deformations during the transport of drug-laden liposomes and temperature-induced deformations during the delivery of the drug. These ideas lay in the coupling of elasticity with hydrodynamics. Experimentally we will use fluorescence microscopy to monitor the local state of the liposomes and we will use nano-indentation to probe mechanical properties of the liposomes. Techniques in microfibration will be developed to study the transport of these objects in microchannels.This research project will be integrated with a curriculum being developed at the University of Illinois at Urbana-Champaign such as the newly developed graduate program in bioengineering and the secondary option of biomechanics newly introduced by the PI in the department of mechanics. The main interest of this course is the study of cell and tissue mechanics where biologists are exposed to engineering methods and engineering students are exposed to protocols of cell biology.