Blood-vessel closure using photosensitizers engineered for two-photon excitation

The spatial control of optical absorption provided by two-photon excitation has led to tremendous advances in microscopy(1) and microfabrication(2). Medical applications of two-photon excitation in photodynamic therapy(3,4) have been widely suggested(5-18), but thus far have been rendered impractical by the low two-photon cross-sections of photosensitizer drugs (which are compounds taken up by living tissues that become toxic on absorption of light). The invention of efficient two-photon activated drugs will allow precise three-dimensional manipulation of treatment volumes, providing a level of targeting unattainable with current therapeutic techniques. Here we present a new family of photodynamic therapy drugs designed for efficient two-photon excitation and use one of them to demonstrate selective closure of blood vessels through two-photon excitation photodynamic therapy in vivo. These conjugated porphyrin dimers have two-photon cross-sections that are more than two orders of magnitude greater than those of standard clinical photosensitizers(17). This is the first demonstration of in vivo photodynamic therapy using a photosensitizer engineered for efficient two-photon excitation.