In recent years several review articles and books have been published on the use of porphyrin-based compounds in photodynamic therapy (PDT). This critical review is focused on (i) the basic concept of PDT, (ii) advantages of long-wavelength absorbing photosensitizers (PS), (iii) a brief discussion on recent advances in developing PDT agents, and (iv) the various synthetic strategies designed at the Roswell Park Cancer Institute, Buffalo, for developing highly effective long-wavelength PDT agents and their utility in constructing the conjugates with tumor-imaging and therapeutic potential (Theranostics). The clinical status of certain selected PDT agents is also summarized (205 references).

We investigate the photoconversion of aqueous 8 nm Ag nanocrystal seeds into 70 nm single crystal plate nanoprisms. The process relies on the excitation of Ag surface plasmons. The process requires dioxygen, and the transformation rate is first-order in seed concentration. Although citrate is necessary for the conversion, and is consumed, the transformation rate is independent of citrate concentration. We propose a mechanism that accounts for these features by coupling the oxidative etching of the seed and the subsequent photoreduction of aqueous Ag(+). The reduced Ag deposits onto a Ag prism of specific size that has a cathodic photovoltage resulting from plasmon "hot hole" citrate photo-oxidation. This photovoltage mechanism also explains recent experimental results involving single and dual wavelength irradiation and the core/shell synthesis of Ag layers on Au seeds.

We report a novel nanoformulation of a photosensitizer (PS), for photodynamic therapy (PDT) of cancer, where the PS molecules are covalently incorporated into organically modified silica (ORMOSIL) nanoparticles. We found that the covalently incorporated PS molecules retained their spectroscopic and functional properties and could robustly generate cytotoxic singlet oxygen molecules upon photoirradiation. The synthesized nanoparticles are of ultralow size ( approximately 20 nm) and are highly monodispersed and stable in aqueous suspension. The advantage offered by this covalently linked nanofabrication is that the drug is not released during systemic circulation, which is often a problem with physical encapsulation. These nanoparticles are also avidly uptaken by tumor cells in vitro and demonstrate phototoxic action, thereby highlighting their potential in diagnosis and PDT of cancer.

Methyl 3-(1'-m-iodobenzyloxyethyl)-3-devinylpyropheophorbide-a (2), obtained in a sequence of reactions from pyropheophorbide-a (a chlorophyll-a derivative), was found to be a promising imaging agent and a photosensitizer for photodynamic therapy (PDT). The electrophilic aromatic iodination of the corresponding trimethylstannyl intermediate with Na124I in the presence of an Iodogen bead afforded 124I-labeled photosensitizer 4 with >95% radioactive specificity. In addition to drug-uptake, the light fluence and fluence rate that were used for the light treatment had a significant impact in long-term tumor cure. The iodo photosensitizer 2 (nonlabeled analogue of 4) produced 100% tumor cure (5/5 mice were tumor free on day 60) at a dose of 1.5 micromol/kg and a light dose of 128 J/cm2, 14 mW/cm2 for 2.5 h (lambda(max) 665 nm) at 24 h postinjection. The photosensitizer also showed promising tumor fluorescence and PET imaging ability. Our present work demonstrates the utility of the first 124I-labeled photosensitizer as a "multimodality agent", which could further be improved by using more tumor-avid and/or target-specific photosensitizers.

The photochemical and electrochemical properties of four chlorin-C60 or porphyrin-C60 dyads having the same short spacer between the macrocycle and the fullerene are examined. In contrast with all the previous results on porphyrin-fullerene dyads, the photoexcitation of a zinc chlorin-C60 dyad results in an unusually long-lived radical ion pair which decays via first-order kinetics with a decay rate constant of 9.1 x 10(3) x s(-1). This value is 2-6 orders of magnitude smaller than values reported for all other porphyrin or chlorin donor-acceptor of the molecule dyad systems. The formation of radical cations of the donor part and the radical anion of the acceptor part was also confirmed by ESR measurements under photoirradiation at low temperature. The photoexcitation of other dyads (free-base chlorin-C60, zinc porphyrin-C60, and free-base porphyrin-C60 dyads) results in formation of the ion pairs which decay quickly to the triplet excited states of the chlorin or porphyrin moiety via the higher lying radical ion pair states as is expected from the redox potentials.

The purpose of this review is to call attention in the use of chlorophyll-a and bacteriochlorophyll-a to develop more than 600 photosensitizers (lambda (max) 660 nm-800 nm) during the last 15 years (1990-2005) at the Photodynamic Therapy Center, Roswell Park Cancer Institute, Buffalo. This article mainly includes the chemistry, preclinical results, and brief clinical data of some of the most effective photosensitizers. The utility of the tumor-avid photosensitizers in developing multimodality agents (imaging and therapy) is also presented.

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