Fluorine-Containing Taxoid Anticancer Agents and Their Tumor-Targeted Drug Delivery.
A long-standing problem of conventional chemotherapy is the lack of tumor-specific treatments. Traditional chemotherapy relies on the premise that rapidly proliferating cancer cells are more likely to be killed by a cytotoxic agent. In reality, however, cytotoxic agents have very little or no specificity, which leads to systemic toxicity, causing undesirable severe side effects. Consequently, various "molecularly targeted cancer therapies" have been developed for use in specific cancers, including tumor-targeting drug delivery systems. In general, such a drug delivery system consists of a tumor recognition moiety and a cytotoxic "warhead" connected through a "smart" linker to form a conjugate. When a multi-functionalized nanomaterial is used as the vehicle, a "Trojan Horse" approach can be used for mass delivery of cytotoxic "warheads" to maximize the efficacy. Exploitation of the special properties of fluorine has proven successful in the development of new and effective biochemical tools as well as therapeutic agents. Fluorinated congeners can also serve as excellent probes for the investigation of biochemical mechanisms.19F-NMR can provide unique and powerful tools for mechanistic investigations in chemical biology. This account presents our recent progress, in perspective, on the molecular approaches to the design and development of novel tumor-targeted drug delivery systems for new generation chemotherapy by exploiting the unique nature of fluorine.
Department of Chemistry, State University of New York at Stony Brook, Stony Brook, NY, 11794-3400.
Joshua
J
Seitz
Jacob G
JG
Vineberg
Edison S
ES
Zuniga
Iwao
I
Ojima
Anticancer agents; Carbon nanotube; Dendrimers; Disulfide linker; Drug delivery system; Fluorescent probe; Fluorine probe; Fluorotaxoid; PET; Taxoid; Tumor-targeted