title: Asymmetric ZnPc-rhodamine B conjugates for mitochondrial targeted photodynamic therapy.
abstract: Design, synthesis, characterization, and photodynamic activity of mitochondria specific asymmetric ZnPc-Rh B conjugates are described. Conjugation of asymmetric ZnPc-OH chromophores 3a and 3b with rhodamine B via the corresponding DIC-activated ester gave the desired near IR-absorbing asymmetric ZnPc-Rh B conjugates 1a and 1b. Conjugates 1a and 1b were shown to produce singlet oxygen upon illumination in DMSO, MeOH and THF. Fluorescence aggregation studies of the dyes 1a, 1b, 3a and 3b in DMSO and phosphate buffered saline (PBS) solution showed that conjugates 1a and 1b were less aggregated compared to the corresponding non-conjugates 3a and 3b suggesting that incorporation of Rh B lowered aggregation of the conjugates in the PBS solution. The four dyes studied have logD7.4 values between 2.31 and 2.48, with the sulfur-containing conjugate 1b being the most hydrophobic. All the dyes showed negligible dark toxicity when colon 26 cells were treated with 5 μM of the dyes while 10-15% cell death was observed for dye concentrations of 15 μM. Illumination (700±40 nm, 45 J/cm(2), 15 min) of the cells ([dye]=15 μM) gave 70% cell death for ZnPc-Rh B conjugates 1a and 1b while no killing for non-conjugates 3a and 3b suggesting that the incorporation of the Rh B in the photosensitizer lowered the aggregation and subsequently improved cellular uptake and phototoxicity.
authors.affiliation: Department of Chemistry and Biochemistry, The University of Arizona, Tucson, AZ 85721, United States.
authors.forename: Dominic K
authors.initials: DK
authors.lastname: Muli
authors.affiliation: College of Pharmacy, University of Oklahoma Health Science Center, Oklahoma City, OK 73117, United States.
authors.forename: Pallavi
authors.initials: P
authors.lastname: Rajaputra
authors.affiliation: College of Pharmacy, University of Oklahoma Health Science Center, Oklahoma City, OK 73117, United States.
authors.forename: Youngjae
authors.initials: Y
authors.lastname: You
authors.affiliation: Department of Chemistry and Biochemistry, The University of Arizona, Tucson, AZ 85721, United States. Electronic address: mcgrath@email.arizona.edu.
authors.forename: Dominic V
authors.initials: DV
authors.lastname: McGrath
mesh_terms: D016923:Cell Death / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D006801:Humans; D007211:Indoles / Q000737:chemistry / Q000494:pharmacology*; D061986:MCF-7 Cells; D008928:Mitochondria / Q000187:drug effects* / Q000378:metabolism / Q000528:radiation effects*; D015394:Molecular Structure; D009942:Organometallic Compounds / Q000737:chemistry / Q000494:pharmacology*; D010778:Photochemotherapy; D017319:Photosensitizing Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D012235:Rhodamines / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship
chemical_list: D007211:Indoles; D009942:Organometallic Compounds; D017319:Photosensitizing Agents; D012235:Rhodamines; C063072:zinc(II) phthalocyanine trisulfonic acid; C029773:rhodamine B
keywords: Anticancer therapy; Asymmetric zinc phthalocyanine; Mitochondria targeting conjugates; Near IR absorption; Photodynamic therapy