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

关键的药效学和药代动力学问题 临床相关喜树碱抗癌药物的治疗作用 药物和新开发的类似物将使用这两种方法进行研究 单光子和双光子激发(TPE)荧光光谱和 成像方法。喜树碱是一种非常有活力的药物 生物系统；它们经历水解性反应和代谢反应 几个类似物与人类白蛋白广泛相互作用。这个 水解反应和白蛋白结合导致活性丧失。 优化喜树碱的治疗活性将受益于 保持药物活性的给药途径 内酯形式。在这项提案中，我们描述了受控释放 将活性药物输送到肿瘤的方法。我们还描述了 成像方法将使我们能够表征 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 一些喜树碱在激发态寿命中表现出显著的变化 在开环和蛋白质结合后，可能不仅可以 测量药物在肿瘤部位的积聚，也测量药物的释放 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.