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

关键的药效学和药代动力学问题

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.