title: Nanocarrier-assisted sub-cellular targeting to the site of mitochondria improves the pro-apoptotic activity of paclitaxel.
abstract: Many drug molecules exert their biological action on intracellular molecular targets present on or inside various cellular organelles. Consequently, it has become more evident that the efficiency and efficacy of drug action is dependent largely on how well an unaided drug molecule is able to reach its intracellular target. We hypothesized that the biological action of such drug molecules might be improved by specific delivery to the appropriate sub-cellular site by a pharmaceutical carrier designed for the purpose. To test our hypothesis, we used paclitaxel, a molecule that has recently been shown to have pro-apoptotic biological targets on the mitochondria but has a quantitative structure-activity relationship-predicted cytosolic accumulation and no affinity for mitochondria. Using a mitochondria-specific nanocarrier system (DQAsomes) prepared from the amphiphilic quinolinium derivative dequalinium chloride to deliver paclitaxel to mitochondria in cells, we report that it is possible to improve the pro-apoptotic action of paclitaxel.
authors.affiliation: Department of Pharmaceutical Sciences, Bouve College of Health Sciences, Northeastern University, 360 Huntington Avenue, Boston, MA 02115, USA. g.d'souza@neu.edu
authors.forename: Gerard G M
authors.initials: GG
authors.lastname: D'Souza
authors.forename: Shing-Ming
authors.initials: SM
authors.lastname: Cheng
authors.forename: Sarathi V
authors.initials: SV
authors.lastname: Boddapati
authors.forename: Richard W
authors.initials: RW
authors.lastname: Horobin
authors.forename: Volkmar
authors.initials: V
authors.lastname: Weissig
mesh_terms: D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage* / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects*; D045744:Cell Line, Tumor; D004337:Drug Carriers; D016503:Drug Delivery Systems; D006801:Humans; D008856:Microscopy, Fluorescence; D053758:Nanoparticles; D017239:Paclitaxel / Q000008:administration & dosage* / Q000494:pharmacology; D021281:Quantitative Structure-Activity Relationship; D013347:Subcellular Fractions / Q000378:metabolism*
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D004337:Drug Carriers; D017239:Paclitaxel