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

Abstract

The spatial control of optical absorption provided by two-photon excitation has led to tremendous advances in microscopy1 and microfabrication2. Medical applications of two-photon excitation in photodynamic therapy3,4 have been widely suggested5,6,7,8,9,10,11,12,13,14,15,16,17,18, 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 photosensitizers17. This is the first demonstration of in vivo photodynamic therapy using a photosensitizer engineered for efficient two-photon excitation. Two-photon excitation is attractive for photodynamic therapy as it potentially allows deeper penetration within biological tissue and targeting with better precision. However, two-photon cross-sections of light-sensitive drugs are typically small, which has until now limited their practical utility. Now Anderson and colleagues have come up with a new family of light-sensitive drugs that are designed for efficient two-photon excitation. They demonstrate selective closure of blood vessels in mice using one of their new drugs.