Photothermal therapy using laser light and exogenous photoabsorbers has an important clinical limitation: it must be performed under the guidance of magnetic resonance thermometry, which is cumbersome and expensive. For photothermal therapy to be widely adopted, an alternative imaging method is a clinical must-have. Photoacoustic imaging is a possible solution when combined with a photoabsorber that is also a photoacoustic sensor for temperature. To generate a thermally responsive optical system, the natural photoagent bacteriopheophorbide a was conjugated to a phospholipid (BChl-lipid) and self-assembled into liposomes. Within the lipid shell of these nanoparticles, BChl-lipid aligns head-to-tail, shifting the Qy (S0-S1) absorption band from 750 nm to 824 nm and increasing the peak extinction 2-fold, all characteristics of J-aggregation. The liposomal BChl-lipid is also fluorescently quenched by ~90%, and is, therefore, photothermally and photoacoustically active. As a nanostructure-dependent phenomenon, BChl-lipid J-aggregation is influenced by lipid membrane fluidity and so the absorption peak at 824 nm is lost when the lipid transition temperature, defined by the lipid tail length, is exceeded. Loss of the ratiometric photoacoustic signal at 824 nm / 750 nm during laser irradiation at 824 nm indicates that the target temperature has been reached. Optical and structural studies demonstrate that BChl-lipid J-aggregation is a dynamic system, with temperature influencing light-to-heat conversion before the transition temperature is reached. Further, protein adsorption in biological environments also impacts the J-aggregate optical stability and sharpness of the thermal transition, which can be moderated through control of the liposome formulation. Application of this responsive photoabsorber to photothermal therapy with real-time photoacoustic imaging guidance will be discussed within this physical context, and guidelines for its integration into current biophotonics methods will be considered.

Photoacoustic alternative to MR thermometry during photothermal therapy

256th National Meeting (2018)

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