1 & 2 PHOTON FLUORESCENCE IMAGE CAMPTOTHECIN ANTICANCER DRUGS & DRUG CARRIERS

关于药物的关键药效学和药代动力学问题 临床相关的喜树碱抗癌药物的治疗用途 代理商和新开发的类似物将使用这两种研究 单光子和双光子激发（TPE）荧光光谱和 成像方法学。 喜树碱是一种非常活跃的药物， 生物系统;它们经历水解和代谢反应 并且几种类似物与人白蛋白广泛地相互作用。 的 水解反应和白蛋白结合导致活性损失。 喜树碱治疗活性的优化将受益于 维持药物活性的药物递送方法 内酯形式。 在本提案中，我们描述了控制释放 用于将活性药物递送至肿瘤的方法。 我们还描述 成像方法，这将使我们能够表征 药物在肿瘤部位的积聚，以及了解 关于肿瘤部位药物状态的详细信息。 因为 一些喜树碱显示出激发态寿命显著变化 在开环和蛋白质结合时，可能不仅 测量肿瘤部位的药物蓄积， 从粒子载体的速率。

Crucial pharmacodynamic and pharmacokinetic issues regarding the therapeutic utilities of clinically-relevant camptothecin anticancer agents and newly developed analogues will be investigated using both one- and two-photon excitation (TPE) fluorescence spectroscopic and imaging methodologies. The camptothecins are very dynamic drugs in biological systems; they undergo hydrolytic and metabolic reactions and several analogues interact with human albumin extensively. The hydrolysis reactions and albumin binding result in a loss of activity. Optimization of camptothecin therapeutic activities will benefit from drug delivery approaches which maintain the drugs in their active lactone forms. In this proposal we describe controlled release approaches for delivering active drug to tumor. We also describe imaging methodologies which will enable us to characterize the accumulation of drug at the tumor site, as well as to understand details concerning the state of the drug at the tumor site. Because some camptothecins exhibit marked changes in excited-state lifetimes upon ring-opening and protein binding, it may be possible not only to measure drug accumulation at the tumor site but also drug release rates from the particle carriers.