Self-Sensing Porphysomes for Fluorescence-Guided Photothermal
Therapy
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Abstract
Porphysomes are highly quenched unilamellar
porphyrin–lipid
nanovesicles with structurally dependent photothermal properties.
The high packing density of porphyrin molecules in the lipid bilayer
enables their application in photothermal therapy, whereas the partial
disruption of the porphysome structure over time restores the porphyrin
fluorescence and enables the fluorescence-guided photothermal ablation.
This conversion is a time-dependent process and cannot be easily followed
using existing analytical techniques. Here we present the design of
a novel self-sensing porphysome (FRETysomes) capable of fluorescently
broadcasting its structural state through Förster resonance
energy transfer. By doping in a near-infrared emitting fluorophore,
it is possible to divert a small fraction of the absorbed energy toward
fluorescence emission which provides information on whether the vesicle
is intact or disrupted. Addition of bacteriopheophorbide–lipid
into the vesicle bilayer as a fluorescence acceptor (0.5–7.5
mol %) yields a large separation of 100 nm between the absorption
and fluorescence bands of the nanoparticle. Furthermore, a progressive
increase in FRET efficiency (14.6–72.7%) is observed. Photothermal
heating and serum stability in FRETysomes is comparable with the undoped
porphysomes. The fluorescence arising from the energy transfer between
the donor and acceptor dyes can be clearly visualized <i>in vivo</i> through hyperspectral imaging. By calculating the ratio between
the acceptor and donor fluorescence, it is possible to determine the
structural fate of the nanovesicles. We observe using this technique
that tumor accumulation of structurally intact porphyrin–lipid
nanovesicles persists at 24 and 48 h postinjection. The development
of FRETysomes offers a unique and critical imaging tool for planning
porphysome-enabled fluorescence-guided photothermal treatment, which
maximizes light-induced thermal toxicity