Guoyu Jiang

Mitochondria-targeting properties and photodynamic activities of porphyrin derivatives bearing cationic pendant

Four meso-tetraphenylporphyrin derivatives bearing either triphenylphosphonium ion-(P1 and P2) or triethylammonium ion-(P3 and P4) terminated alkoxy group at either para-(P1 and P3) or meta-(P2 and P4) position of one meso-phenyl group were designed and synthesized. P1-P4 show similar absorption and fluorescence emission spectra and (1)O(2) quantum yields. The more lipophilic nature of triphenylphosphonium ion over triethylammonium ion renders P1 and P2 higher octanol/water partition coefficients than P3 and P4. Confocal fluorescence microscopy proved that P1-P4 are all mitochondria-targeting. MTT assay showed that P1-P4 presented significant phototoxicity at the concentrations that dark toxicity is negligible towards human breast cancer cell line MCF-7 cells, displaying their application potential in PDT.

Greatly enhanced binding of a cationic porphyrin towards bovine serum albumin by cucurbit[8]uril

Binding affinity towards serum albumin and intracellular proteins is of importance for a photodynamic therapy (PDT) sensitizer to selectively localize in tumours and efficiently induce cell death. In this paper, it was found that cucurbit[8]uril (CB8) can greatly improve the binding affinity of 5,10,15,20-tetrakis(1-methyl-4-pyridinio)porphyrin tetra(p-toluenesulfonate) (TMPyP), a promising PDT photosensitizer, towards bovine serum albumin (BSA). Absorption, fluorescence emission, (1)H NMR, dynamic light scattering, atomic force microscope, as well as protein photocleavage measurements suggest that the binding enhancement originates from the formation of a ternary complex of CB8·TMPyP·tryptophan residues. This finding opens up a new approach for the development of more efficient PDT agents.

Selective Photodynamic Inactivation of Bacterial Cells over Mammalian Cells by New Triarylmethanes

Three new triarylmethane dyes (TAMs), MPCV, DPCV, and AEV, were synthesized and their photodynamic inactivation abilities against E. coli and human pulmonary carcinoma A549 cells were compared to two commercial TAMs, CV and EV. The enhanced hydrophilicity of MPCV and AEV decreases their cellular uptake to A549 cells dramatically. However, their binding affinity toward E. coli cells are comparable to that of CV and EV by virtue of the improved electrostatic attraction with highly negatively charged E. coli outer membranes. MPCV and AEV were also found to generate hydroxyl radicals more efficiently upon irradiation than CV and EV. Consequently, MPCV and AEV exhibited markedly improved photodynamic inactivation of E. coli cells but remarkably diminished photodynamic inactivation of A549 cells than CV and EV. The photodynamic inactivation ability of DPCV was much lower than that of CV due to its high propensity for bleaching in neutral aqueous solution. Our work demonstrates that the introduction of protonatable groups in a proper manner into the structures of TAMs may lead to selective binding and photodynamic inactivation toward bacterial cells over mammalian cells. This strategy may be extended to other types of photodynamic antimicrobial chemotherapy (PACT) agents to improve their clinical potential.

The synthesis and 1O2 photosensitization of halogenated asymmetric aniline-based squaraines

The halogenated (brominated or iodinated) squaraines have promising potential in the application of photodynamic therapy (PDT). Though aniline-based squaraines are the most classical squaraine dyes, no halogenated derivatives with the halogen atoms directly incorporated in the conjugation skeleton of the squaraine chromophore have been reported so far. In this work, a stepwise synthetic approach, i.e. by way of the halogenated semi-squaraines, was applied successfully to prepare halogenated asymmetric aniline-based squaraines. Such a structure makes iodine atoms be able to exert significant heavy atom effect on the intersystem crossing (ISC) efficiency of the squaraine dye. As a result, the iodinated asymmetric squaraine (SQ–OH–I) exhibits a singlet oxygen (1O2) quantum yield as high as 0.54. In contrast, the 1O2 quantum yield of the non-halogenated squaraine analogue (SQ–OH) is only 0.02.

Host–Guest Interaction of Hoechst 34580 and Cucurbit[7]uril

To track nuclear dynamic processes by fluorescence imaging, nuclear stains should be highly fluorescent, resistant to photobleaching, and inert to nuclear processes. The nuclear stains of the Hoechst family, such as Hoechst 34580, show bright fluorescence only on groove binding to DNA, and therefore may interfere with visualization of nuclear dynamic processes induced by other stimuli. We study host-guest interactions between Hoechst 34580 and Cucurbit[7]uril (CB7) in aqueous solutions. The formation of CB7-Hoechst 34580 inclusion complexes with stoichiometry of 2:1 in water and 1:1 in phosphate-buffered saline (PBS) solution (pH 7.0) is confirmed by (1)H NMR, absorption spectra, fluorescence spectra, MALDI-TOF MS, and molecular modeling. Compared to Hoechst 34580, the inclusion complex exhibits redshifted absorption, intensified fluorescence, improved photostability, weakened DNA binding affinity, comparable ability to penetrate cell nuclei, and better nuclear-staining capability, and thus a new avenue for the application of cucurbituril in fluorescence imaging is opened.

A ferrocenyl pyridine-based Ru(II) arene complex capable of generating ·OH and 1O2 along with photoinduced ligand dissociation

Photoactivated chemotherapy (PACT) and photodynamic therapy (PDT) are two types of cancer treatment modalities that rely on photoinduced ligand dissociation and photosensitized or photocatalyzed reactive oxygen species (ROS) generation to realize anticancer activities with high selectivity, respectively. In this study, a novel Ru complex, [(p-cym)Ru(bpy)(py-Fc)]2+ (1), where p-cym = para-cymene, bpy = 2,2′-bipyridine, and py-Fc = 4-pyridyl ferrocene, was demonstrated to show dual activity from PACT and PDT. 1 has a long-wavelength absorption band extending to 600 nm and can generate both hydroxyl radicals (·OH) and singlet oxygen (1O2) along with photoinduced monodentate ligand dissociation. As a result, 1 displays DNA photocleavage activity as well as phototoxicity against human ovarian adenocarcinoma cells SKOV3 and human lung adenocarcinoma cells A549. The underlying mechanisms were discussed by comparing the photophysical, photochemical, and photobiological properties of 1 with that of [(p-cym)Ru(bpy)(py)]2+ (2, py = pyridine) and free py-Fc, providing guidelines for developing new photoactivated metallodrugs with multiple functions.

Self-Assembly of Anionic Porphyrins and Alkaline or Alkaline Earth Metal Ions Mediated by Cucurbit[7,8]uril

Nanoscaled coordination polymers based on biologically prevalent ions have potential applications in drug delivery and biomedical imaging. Herein, coordination polymer nanoparticles of anionic porphyrins, including meso-tetra(4-carboxyphenyl)-porphyrin (H2 TCPP(4-)) and meso-tetra(4-sulfonatophenyl)-porphyrin (H2 TPPS(4-)), and alkaline or alkaline earth metal cations, such as K(+) and Ca(2+), were constructed in aqueous solution in the presence of cucurbit[7]uril (CB7) or cucurbit[8]uril (CB8). UV/Vis absorption and fluorescence spectroscopy, dynamic light scattering (DLS), scanning electron spectroscopy (SEM), and atomic force microscopy (AFM) were applied to explore the assembly and particle formation of porphyrin anions and metal cations mediated by CBn. The particle size depends on the kinds of CBn and metal cations and their concentrations. The uptake of H2 TPPS(4-) particles by tumor cells (A549 cells) was found to be more efficient than H2 TPPS(4-) at 37 °C, showing the application potential of such assembled particles in biology and medicine.

An upconversion nanoparticle/Ru(II) polypyridyl complex assembly for NIR-activated release of a DNA covalent-binding agent

Photoactivated anticancer chemotherapy distinguishes itself by its high selectivity by virtue of the spatiotemporal control of irradiation. However, short photoactivation wavelengths limit its application. Herein, an amphiphilic Ru(II) complex, cis-[Ru(bpy)2(C18H37CN)2]2+ (bpy = 2,2′-bipyridine), was embedded along with a poly(ethylene glycol, PEG)-modified lipid onto the surfaces of oleate-capped lanthanide-doped upconversion nanoparticles (UCNPs). The resultant core–shell hybrid system is water-dispersible, stable in the dark, and releases a DNA covalent-binding agent of [Ru(bpy)2(H2O)2]2+ upon 980 nm laser irradiation, providing guidelines for developing near-infrared (NIR) light triggered chemotherapeutics.

Photodynamic inactivation of Escherichia coli by porphyrin cytochrome c

The positively charged porphyrin cytochrome c (porphyrin Cyt c) was found to be able to bind to Escherichia coli, and showed efficient antimicrobial activity upon visible light irradiation, opening avenues for the development of protein-loaded photoinactivation agents against Gram-negative bacteria.