Highly Efficient Singlet Oxygen Generators Based on Ruthenium Phthalocyanines: Synthesis,Characterization and in vitro Evaluation for Photodynamic Therapy

The synthesis of ruthenium(II) phthalocyanines (RuPcs) endowed with one carbohydrate unit—that is, glucose, galactose and mannose—and a dimethylsulfoxide (DMSO) ligand at the two axial coordination sites, respectively, is described. Two series of compounds, one unsubstituted at the periphery, and the other one bearing eight PEG chains at the isoindole meta-positions, have been prepared. The presence of the axial DMSO unit significantly increases the phthalocyanine singlet oxygen quantum yields, related to other comparable RuPcs. The compounds have been evaluated for PDT treatment in bladder cancer cells. In vitro studies have revealed high phototoxicity for RuPcs unsubstituted at their periphery. The phototoxicity of PEG-substituted RuPcs has been considerably improved by repeated light irradiation. The choice of the axial carbohydrate introduced little differences in the cellular uptake for both series of photosensitizers, but the phototoxic effects were considerably higher for compounds bearing mannose units.     

Homo‐ and Heteroleptic Phototoxic Dinuclear Metallo‐Intercalators Based on RuII(dppn) Intercalating Moieties: Synthesis,Optical, and Biological Studies

Using a new mononuclear “building block,” for the first time, a dinuclear Ru^II(dppn) complex and a heteroleptic system containing both Ru^II(dppz) and Ru^II(dppn) moieties are reported. The complexes, including the mixed dppz/dppn system, are ¹O₂ sensitizers. However, unlike the homoleptic dppn systems, the mixed dppz/dppn complex also displays a luminescence “switch on” DNA light‐switch effect. In both cisplatin sensitive and resistant human ovarian carcinoma lines the dinuclear complexes show enhanced uptake compared to their mononuclear analogue. Thanks to a favorable combination of singlet oxygen generation and cellular uptake properties all three of the new complexes are phototoxic and display potent activity against chemotherapeutically resistant cells.     

Pyridinium‐Substituted TetraphenylethyleneEntailing Alkyne Moiety: Enhancement of Photosensitizing Efficiency and Antimicrobial Activity

Apart from sensing and imaging, luminogens with aggregation‐induced emission (AIE) are also interesting for photosensitizing. The photosensitizing behavior and bacteria‐killing performance of a pyridinium‐substituted tetraphenylethylene with an alkyne group ( TPE‐A‐Py⁺ ) is reported herein. Interestingly, TPE‐A‐Py⁺ exhibits higher photosensitizing efficiency than TPE‐Py⁺ (without alkyne group) when I⁻ was used as a counteranion. This is well explained by the fact that the ΔΕ _ST between the excited singlet state (S ₁) and triplet state (T ₁) was lower for TPE‐A‐Py⁺ than for TPE‐Py⁺ , according to theoretical calculations. Moreover, replacement of I ⁻ with other anions (PF₆⁻, N(SO₂CF₃)₂⁻ and BPh₄⁻) led to a decrease of photosensitizing efficiency for TPE‐A‐Py⁺ . Notably, TPE‐A‐Py⁺ could be used as an efficient photosensitizer to photo‐inactivate ampicillin‐resistant (amp^r) E. coli at low concentration under white‐light irradiation very quickly.     

Size and Shape Effects of Near-Infrared Light-Activatable Cu2(OH)PO4 Nanostructures on Phototherapeutic Destruction of Drug-Resistant Hypoxia Tumors

Development of simple, robust, and noninvasive therapeutic approaches to treat cancers and improve survival rates is a grand challenge in clinical biomedicine. In particular, the sizes and shape of the nanomaterials play a vital role in dictating their biodistribution and clearance pathways. It remains elusive how the size and shape of a nanomaterial affect its therapeutic efficacy in cancer diagnosis and treatments. To tackle the above problem, the effects of size and shape of Cu₂(OH)PO₄ nanostructures (nanosheets and quantum dots) on the photodynamic therapy (PDT) in destroying malignant drug-resistant lung tumors and on combating the tumor hypoxia problem are investigated and compared. The photocatalytic mechanism of Cu₂(OH)PO₄ nanostructures mainly involves the generation of reactive oxygen species (ROS), such as hydroxyl radical (^·OH) and singlet oxygen (¹O₂). Under an oxygen deprivation condition, Cu₂(OH)PO₄ nanosheets still can generate OH radicals to kill cancer cells upon near-infrared (NIR) light irradiation. Overall, in vitro and in vivo experiments show that Cu₂(OH)PO₄ nanosheets can overcome tumor hypoxia problems and effectively mediate dual modal PDT and photothermal therapeutic (PTT) effects on destruction of NCI-H23 lung tumors in mice using ultralow doses (350 mW cm⁻²) of NIR (915 nm) light.     

Function of Tetrapyrroles,Regulation of Tetrapyrrole Metabolism and Methods for Analyses of Tetrapyrroles

Tetrapyrroles are essential cofactors and pigments. Photosynthetic organisms share the use of the highest diversity of tetrapyrrole end products. This report intends to call readers’ attention to the recent achievements in research on tetrapyrrole biosynthesis and the current hot topics in tetrapyrrole biosynthesis, including posttranslational control mechanisms and intracellular signaling between the nucleus and the two organelles, plastids and mitochondria. Moreover, the functions of tetrapyrroles in the photosynthetic organisms and valuable information about the current analytical techniques to determine steady state levels of tetrapyrrole intermediates from cyanobacteria, green algae and plant will be surveyed.     

Non‐aggregated boron–fluorine derivatives with photodynamic activity

Novel non‐aggregated boron–fluorine derivatives with large Stokes shift were facilely synthesized and characterized. These dyes show moderate absorptive coefficients and intense fluorescence emission, and excellent photo‐stability in solvents and also in solid state. According to X‐ray single‐crystal analysis, non‐covalent intermolecular interactions provide a rigid structure, which inhibits aggregate formation. These non‐aggregated dyes can generate singlet oxygen under light irradiation, which makes them good candidates for photodynamic therapy. Copyright © 2012 John Wiley & Sons, Ltd.     

A Self‐Assembled Metallomacrocycle Singlet Oxygen Sensitizer for Photodynamic Therapy

Although metal‐ion‐directed self‐assembly has been widely used to construct a vast number of macrocycles and cages, it is only recently that the biological properties of these systems have begun to be explored. However, up until now, none of these studies have involved intrinsically photoexcitable self‐assembled structures. Herein we report the first metallomacrocycle that functions as an intracellular singlet oxygen sensitizer. Not only does this Ru₂Re₂ system possess potent photocytotoxicity at light fluences below those used for current medically employed systems, it offers an entirely new paradigm for the construction of sensitizers for photodynamic therapy.     

纳米材料在肿瘤光动力治疗中的研究进展

光动力治疗是新兴的非侵入性癌症治疗方法。纳米材料以其独特的结构以及光物理、光化学性质成为可用于光动力治疗的光敏剂。根据纳米材料的不同种类,分别对无机非金属纳米材料、无机金属纳米材料、有机小分子纳米材料以及有机聚合物纳米材料等的构建策略及其在光动力治疗肿瘤中的应用进行综述。展望了纳米材料在未来肿瘤光动力治疗中的挑战和发展方向。为新一代纳米光敏剂的构建提供创新思路,并扩展其在癌症治疗中的潜力。     

Elucidation of the Intersystem Crossing Mechanism in a Helical BODIPY for Low‐Dose Photodynamic Therapy

Intersystem crossing (ISC) of triplet photosensitizers is a vital process for fundamental photochemistry and photodynamic therapy (PDT). Herein, we report the co‐existence of efficient ISC and long triplet excited lifetime in a heavy atom‐free bodipy helicene molecule. Via theoretical computation and time‐resolved EPR spectroscopy, we confirmed that the ISC of the bodipy results from its twisted molecular structure and reduced symmetry. The twisted bodipy shows intense long wavelength absorption (?=1.76×10⁵ m ^?1 cm^?1 at 630 nm), satisfactory triplet quantum yield (Φ_T=52 %), and long‐lived triplet state (τ_T=492 μs), leading to unprecedented performance as a triplet photosensitizer for PDT. Moreover, nanoparticles constructed with such helical bodipy show efficient PDT‐mediated antitumor immunity amplification with an ultra‐low dose (0.25 μg kg^?1), which is several hundred times lower than that of the existing PDT reagents.