Departmental Affiliation and City, State, Zip for All Authors

1. College of Natural Sciences, Edinburg, Texas 78541; 2. Institute for Molecular Medicine, Fort Worth, Texas 76107; 3. Institute for Molecular Medicine, Fort Worth, Texas 76107; 4. Institute for Molecular Medicine, Fort Worth, Texas 76107; 5. Institute for Molecular Medicine, Fort Worth, Texas 76107

Scientific Abstract

Valrubicin and Doxorubicin have been used to treat several different types of cancer since the 1970’s. Classified as Anthracyclines, they are known for their activity in inhibiting cell division by intercalating between the nucleotide base pairs of the DNA and RNA sequences; thereby disrupting replication of rapidly growing cancer cells. A more serious mechanism of action provided from these drugs is their effect in the generation of free oxygen radicals, which assist in damaging DNA, but also bring about toxic side effects. Therefore, in order to reduce these systemic side effects brought about by the generation of free radicals, rHDL nanoparticles can be potentially used to help create a target specific drug delivery pathway. Highly proliferating cancer cells require cholesterol for their growth and maintenance. Hence, tumor cells overexpress the Scavenger Receptor B (SRB-1) which is specific to high-density lipoproteins (HDL). This specific study aimed at packing Doxorubicin and Valrubicin into reconstituted high-density lipoprotein (rHDL) nanoparticles and using the drug’s intrinsic fluorescence to characterize loading and encapsulation efficiency. For this study, rHDL nanoparticles were synthesized for both drugs. Several steady state and time resolved measurements such as absorption, emission, excitation, anisotropy, quenching and time resolved lifetime were employed to photophysically characterize Free drug versus rHDL with drug. The overall goal of this project was to use the fluorescent properties of Doxorubicin and Valrubicin to photophysically characterize their association with rHDL nanoparticles. This has potential applications in monitoring site specific drug delivery and uptake using minimal invasive procedures.

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USING FLUORESCENCE SPECTROSCOPY TO EVALUATE DOXORUBICIN AND VALRUBICIN

Valrubicin and Doxorubicin have been used to treat several different types of cancer since the 1970’s. Classified as Anthracyclines, they are known for their activity in inhibiting cell division by intercalating between the nucleotide base pairs of the DNA and RNA sequences; thereby disrupting replication of rapidly growing cancer cells. A more serious mechanism of action provided from these drugs is their effect in the generation of free oxygen radicals, which assist in damaging DNA, but also bring about toxic side effects. Therefore, in order to reduce these systemic side effects brought about by the generation of free radicals, rHDL nanoparticles can be potentially used to help create a target specific drug delivery pathway. Highly proliferating cancer cells require cholesterol for their growth and maintenance. Hence, tumor cells overexpress the Scavenger Receptor B (SRB-1) which is specific to high-density lipoproteins (HDL). This specific study aimed at packing Doxorubicin and Valrubicin into reconstituted high-density lipoprotein (rHDL) nanoparticles and using the drug’s intrinsic fluorescence to characterize loading and encapsulation efficiency. For this study, rHDL nanoparticles were synthesized for both drugs. Several steady state and time resolved measurements such as absorption, emission, excitation, anisotropy, quenching and time resolved lifetime were employed to photophysically characterize Free drug versus rHDL with drug. The overall goal of this project was to use the fluorescent properties of Doxorubicin and Valrubicin to photophysically characterize their association with rHDL nanoparticles. This has potential applications in monitoring site specific drug delivery and uptake using minimal invasive procedures.

Manuscript Number

1007