Date of Award
Doctor of Philosophy
Graduate School of Biomedical Sciences
Doxorubicin, also known as Adriamycin, is an anthracycline antibiotic which first gained clinical prominence in the early 1970’s as an effective antitumor agent. It is still used today to treat a spectrum of cancers like lymphoma, bladder, stomach, lung, breast, ovarian, and several others. Due to its production of free radicals to attack tumor cells, Doxorubicin interferes with mitochondrial phosphorylation and also induces cardiotoxicity. Thus, efficient and biocompatible delivery methods are needed for targeted drug delivery to overcome systemic toxicity. To maintain a high level of growth, tumor cells overexpress Scavenger receptors type B-1 (SR-B1). This cellular characteristic can be used to target and selectively deliver doxorubicin to tumor cells by packing it in reconstituted high density lipoprotein (rHDL) nanoparticles, which bind selectively to SR-B1 receptors. Nanoparticles as target-specific drug delivery agents are increasingly used in cancer therapy to enhance bioavailability and to reduce off target toxicity of anti-cancer agents. Several different formulations of rHDL nanoparticles to incorporate doxorubicin were synthesized. Doxorubicin’s intrinsic fluorescence was used to photophysically characterize the properties of loaded rHDL nanoparticles including absorption, emission, excitation, steady-state and time resolved anisotropy measurements, and quenching to study drug shielding by nanoparticles. Overall the fluorescence properties of the rHDL: doxorubicin complex may reveal valuable novel characteristics of this drug delivery vehicle that may be particularly applicable when used in systemic (intravenous) therapy.
"Spectral Properties of Doxorubicin Doped rHDL Nanoparticles" Fort Worth, Tx: University of North Texas Health Science Center;