The control of luminous radiation has extremely important implications for modern and future technologies as well as in medicine. In this Review, we detail chemical structures and their relevant photophysical features for various groups of materials, including organic dyes such as metalloporphyrins and metallophthalocyanines (and derivatives), other common organic materials, mixed metal complexes and clusters, fullerenes, dendrimeric nanocomposites, polymeric materials (organic and/or inorganic), inorganic semiconductors, and other nanoscopic materials, utilized or potentially useful for the realization of devices able to filter in a smart way an external radiation. The concept of smart is referred to the characteristic of those materials that are capable to filter the radiation in a dynamic way without the need of an ancillary system for the activation of the required transmission change. In particular, this Review gives emphasis to the nonlinear optical properties of photoactive materials for the functi...

Nonlinear Optical Materials for the Smart Filtering of Optical Radiation.

Photodynamic therapy (PDT) requires a medical device, a photosensitizing drug and adequate use of both to trigger biological mechanisms that can rapidly destroy the primary tumour and provide long-lasting protection against metastasis. We present a multidisciplinary view of the issues raised by the development of PDT. We show how spectroscopy, photophysics, photochemistry and pharmacokinetics of photosensitizers determine the mechanism of cell death and clinical protocols. Various examples of combinations with chemotherapies and immunotherapies illustrate the opportunities to potentiate the outcome of PDT. Particular emphasis is given to the mechanisms that can be exploited to establish PDT as a systemic treatment of solid tumours and metastatic disease.

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Photodynamic therapy (PDT) of cancer: from local to systemic treatment

Engineering of relevant photodynamic processes through structural modifications of metallotetrapyrrolic photosensitizers

Progress in the photodynamic therapy (PDT) of cancer should benefit from a rationale to predict the most efficient of a series of photosensitizers that strongly absorb light in the phototherapeutic window (650–800 nm) and efficiently generate reactive oxygen species (ROS=singlet oxygen and oxygen-centered radicals). We show that the ratios between the triplet photosensitizer–O2 interaction rate constant (kD) and the photosensitizer decomposition rate constant (kd), kD/kd, determine the relative photodynamic activities of photosensitizers against various cancer cells. The same efficacy trend is observed in vivo with DBA/2 mice bearing S91 melanoma tumors. The PDT efficacy intimately depends on the dynamics of photosensitizer–oxygen interactions: charge transfer to molecular oxygen with generation of both singlet oxygen and superoxide ion (high kD) must be tempered by photostability (low kd). These properties depend on the oxidation potential of the photosensitizer and are suitably combined in a new fluorinated sulfonamide bacteriochlorin, motivated by the rationale.

Photodynamic therapy efficacy enhanced by dynamics: the role of charge transfer and photostability in the selection of photosensitizers.

Reactive oxygen species (ROS) play key roles in cell signaling systems and homeostasis, and they are also fundamental to photodynamic therapy (PDT) PDT efficacy can be affected by the nature and persistence of ROS A comprehensive understanding of ROS generation pathways greatly facilitates the analysis of photodynamic mechanisms and enables potentiation of PDT efficacy Diverse methods exist to distinguish between Type I and Type II mechanisms of ROS generation The direct monitoring of 1O2 formation involves the detection of its phosphorescence at 1270 nm Electron spin resonance is also used in conjunction with appropriate spin traps for detection of oxygen-centered radical species Moreover, a variety of more or less specific fluorescent probes are frequently used to detect both singlet oxygen and free radicals This chapter summarizes our recent efforts in the design and characterization of new ROS-generating systems for PDT Special attention is given to bacteriochlorins because they absorb in the NIR, generate ROS via both Type I and Type II mechanisms, and are very efficient in the PDT treatment of several types of tumors including pigmented melanoma The current status and possible opportunities of ROS generation and potentiation in PDT are highlighted Particular emphasis is placed on the elucidation of the ROS-mediated photochemical and molecular mechanisms that give rise to the establishment of PDT as a first-line systemic treatment of highly resistant diseases, especially invasive and metastatic tumors

Reactive Oxygen Species in Photodynamic Therapy: Mechanisms of Their Generation and Potentiation

Amphiphilic meso(sulfonate ester fluoroaryl)porphyrins: refining the substituents of porphyrin derivatives for phototherapy and diagnostics

The ruthenium(II) complex cis-[RuCl2(dmso)4] is known for its antiproliferative properties. This has stimulated the discovery of a wide group of new ruthenium complexes considered as potential anticancer drugs. The stability of these ruthenium complexes under physiological conditions and their interaction with protein amino acid residues are particularly important because of their intravenous administration. The studies presented here are devoted to the stability of cis-[RuCl2(dmso)4] under physiological pH conditions and its reactivity towards L-methionine. Immediate dissociation of one dmso ligand from the parent complex after dilution in water leads to the formation of fac-[RuCl2(H2O)(dmso)3], which under basic conditions undergoes stepwise dissociation of chloride ions without further dmso release. The hydrolysis of fac-[RuCl2(H2O)(dmso)3] at pH 7.4 and also base-catalyzed hydrolysis were investigated in detail by application of kinetic and spectroscopic (UV/Vis, NMR) measurements. The combined experimental and theoretical study revealed that L-methionine coordinates to fac-[RuCl(OH)(H2O)(dmso)3] by substituting a water ligand with simultaneous dmso release. Detailed NMR characterization of the product indicated that methionine coordinates through the NH2 group rather than the thioether moiety. This conclusion was further supported by theoretical calculations with the application of ETS–NOCV analysis.

Agnieszka Adamowicz

Papers

Amphiphilic meso(sulfonate ester fluoroaryl)porphyrins: refining the substituents of porphyrin derivatives for phototherapy and diagnostics

Base-Catalyzed Hydrolysis of a RuII–Chloro–dmso Complex and Its Reactivity towards L-Methionine