Published: May 18, 2011 r2011 American Chemical Society 6503 dx.doi.org/10.1021/jp202436x | J. Phys. Chem. A 2011, 115, 6503–6508 ARTICLE pubs.acs.org/JPCA Influence of Carbohydrate Biological Vectors on the Two-Photon Resonance of Porphyrin Oligomers Fabien Hammerer, †,‡,§ Sylvain Achelle,* ,†,‡,§, Patrice Baldeck, || Philippe Maillard, †,‡,§ and Marie-Paule Teulade-Fichou †,‡,§ † UMR 176 CNRS/Institut Curie, Institut Curie, B^ at 110, Centre Universitaire, Universit  e Paris-Sud, F-91405 Orsay, France ‡ Institut Curie, Section de Recherches, Centre Universitaire, Universit  e Paris-Sud, F-91405 Orsay, France § GDR CNRS 3049 “M edicament Photoactivable À Photochimioth erapie (PHOTOMED)”, IMRCP, UMR 5623, Universit  e Toulouse 3, F-31062 Toulouse Cedex 9, France ) Laboratoire de Spectrom etrie Physique, UMR 5588, Universit  e Joseph Fourier/CNRS, 140 rue de la physique, B.P. 87 38402 Saint Martin d’H eres Cedex, France ’ INTRODUCTION Photodynamic therapy (PDT) is a promising technique for the treatment of various pathologies including cancer, 1À3 skin 4,5 or eye diseases, 6,7 and microbiological infections. 8À10 It involves a photosensitizer (Ps), which, upon absorption of light, reacts with surrounding molecules to produce highly reactive species such as singlet oxygen which, in turn, lead to cell death. 11 The most common Ps used in PDT today are cyclic tetrapyrroles or porphynoids because of their long triplet lifetime. 12 These Ps's have one-photon absorption (1PA) peaks in the visible wave- length range (400À700 nm) but one concern is the low penetration depth of visible light which is strongly absorbed by biological tissues. 13 However, the main components of human skin and tissues absorb less in the red and near IR area of the light spectrum forming what is currently known as the physiological optical window between 700 and 1300 nm. 13,14 Therefore a red- shifted excitation via a simultaneous two-photon absorption (2PA) mechanism would allow both a better penetration of light in the skin and tissue and a better three-dimensional monitoring of the photosensitizing area. 15 A two-photon excitation of tetrapyrrolic macrocycles in their Soret band would fall just inside the physiological optical window. Unfortunately mono- meric porphyrins without donor/acceptor groups have only a small 2PA cross section of less than a few tens of Goeppert- Mayer (GM) . 16 However conjugative extensions via mesoÀmeso conjugated bridges have led to dramatic improvements in the 2PA cross section values for this class of molecules. 17À19 Recent in vivo experiments have shown that PDT performed with PS exhibiting high 2PA enables the treatment of tumors and allows greater precision than is achievable by conventional one-photon excitation as a consequence of the quadratic dependence of two- photon excitation on the local light intensity. 20,21 Taking into account the fact that lectin-type receptors are overexpressed in certain malignant cells 22,23 and that carbohy- drates such as R-mannose and β-galactose have specific interac- tion with these receptors, 24À26 the addition of carbohydrate moieties to a Ps allows the active targeting of malignant cells and increases the selectivity of the treatment as has been shown by our previous studies. 27À29 We have recently described the synthesis of carbohydrateÀporphyrin conjugates with 2PA properties as potential photosensitizing agents for PDT. 30 The 1PA and 2PA spectroscopic properties observed appear different from those previously described by Drobizhev et al. for non- vectorized similar oligomers. 31,32 In this article, we propose a study of the 1PA and 2PA spectroscopic data of carbohydrate- vectorized compounds 1 and 3, and we compare them with the Received: March 15, 2011 Revised: April 30, 2011 ABSTRACT: We propose a spectroscopic study of π-conjugated porphyrin dimers and a triphenylamine centered trimer bearing monoethyleneglycol-peracetylated R-mannose targeting moieties, which were synthesized for application to two-photon absorption photodynamic therapy (2PA-PDT). The collected spectroscopic data are explained through comparison with previous results obtained on similar nonvectorized analogues. It appears that the different shifts and variations in linear and nonlinear absorption and emission bands are mainly due to an increased twist between the tetrapyrrolic units. The 2PA properties of the triphenylamine-centered trimer have been studied, and two fluorescence emission bands are observed that seem to originate from two different 2PA excitation pathways. These results have important implication for the design of new vectorized photosensitizers for 2PA-PDT.