UNS: Intracellular Drug Delivery Mediated by Laser-activated Nanoparticles

这个项目将探索一种使细胞膜暂时可渗透的新方法，使药物分子能够进入细胞并发挥其治疗功能。该方法依赖于用脉冲激光能量照射散布在细胞之间的纳米颗粒。初步数据表明，照射纳米颗粒导致细胞对荧光分子的摄取显著增加，而不丧失细胞活力。这项研究可能会带来一种新的方法，以增强生物分子向目标细胞的传递，用于治疗、诊断和实验室应用。该项目将测试一个假设，即激光能量提高纳米粒子的温度，使周围的液体蒸发，产生局部应力场，可以暂时和非破坏性地渗透细胞膜，从而允许活细胞在细胞内摄取外源分子。一系列实验将量化激光激活纳米颗粒释放能量形式的时空特征，以验证纳米颗粒能量转导的主要特征是快速产生包裹的蒸汽泡，形成后缓慢凝结的假设。该研究还将确定粒子转导输出的哪些特征与细胞内高摄取和细胞活力相关，以验证细胞生物效应由细胞直径尺度上发生的声学和热效应控制的假设。

CBET - 1510028PI: Prausnitz, MarkThis project will explore a novel way to make cell membranes temporarily permeable so that drug molecules are able to enter the cell and carry out their therapeutic functions. The method relies on irradiating nanoparticles interspersed between the cells with pulsed laser energy. Preliminary data show that irradiating the nanoparticles leads to a significant increase in the cellular uptake of a fluorescent molecule without loss of cell viability. The research could lead to a new way to enhance the delivery of biomolecules to targeted cells for therapeutic, diagnostic and laboratory applications.This project will test the hypothesis that the laser energy raises the nanoparticle temperature and vaporizes surrounding liquid, producing local stress fields that can temporarily and non-destructively permeabilize cell membranes, thereby allowing intracellular uptake of exogenous molecules by living cells. A series of experiments will quantify the spatio-temporal characteristics of the forms of energy released by laser-activated nanoparticles to test the hypothesis that the dominant characteristic of energy transduction by a nanoparticle is the rapid generation of an enveloping vapor bubble that condenses slowly after formation. The research also will determine which features of the particle transduction outputs correlate to high intracellular uptake and cell viability to test the hypothesis that cellular bioeffects are controlled by acoustic and thermal effects occurring on the scale of a cell diameter.