Rational Design of Fluorophores for In Vivo Applications - Progress in Molecular Biology and Translational Science - page 87

amphiphilic polymers and hydrophobic porphyrins. 179,182,207 As a result,
vehicles with diameters of 50 nm-50 m m are formed in which porphyrins
are uniformly distributed in the vehicle membrane. As porphyrins stay in
the hydrophobic environment of the vehicle membrane, they retain
optical properties comparable to those in organic solvents. The resulting
highly emissive polymersomes can be freely dispersed in water and have
been used for in vivo imaging, 182 labeling, and in vivo tracking of dendritic
cells. 181
Porphyrin arrays have been also incorporated into the hydrophobic core
of the LDL apo forms, forming nanoparticles highly emissive in water. The
resulting nanoparticles show tumor specificity, as many tumor cells over-
express the LDL receptor. 180 Porphyrin-doped LDLs have been used for
imaging B16 180 melanoma cells. Similarly, bacteriopheophytin a bisoleate
has been incorporated into the hydrophobic core of high-density lipopro-
tein nanoparticles (size 12 nm) and used for in vivo imaging of tumor. 188

5.7. Photocytotoxicity of tetrapyrrolic macrocycle
The use of tetrapyrrolic macrocycles as fluorophores in vivo raises concern
about their phototoxicity. Porphyrins, hydroporphyrins, and phthalocya-
nines upon excitation populate the corresponding triplet excited state,
which reacts with ambient oxygen to produce highly cytotoxic singlet
oxygen and other highly reactive oxygen species. 167-169 This property is
very useful in photodynamic therapy, where tetrapyrrolic macrocycles are
widely used as photosensitizers, but can be potentially detrimental when
one considers using them as fluorophores in living organisms. The
photocytotoxicity depends on the many factors, such as the intrinsic
photochemical properties of the photosensitizer (quantum yield and lifetime
of the triplet state), localization of the photosensitizer inside the tissue, and
the intensity of illumination. In general, even good photosensitizers require
a higher dosage of light to induce phototoxicity than is typically used in
fluorescence imaging experiments. Moreover, it is expected that
tetrapyrrolic macrocycles with optical properties optimized for fluorescence
imaging (i.e., with high quantum yield of fluorescence) would have a lower
quantum yield of the triplet state, as these two processes compete with each
other. For example, it has been reported that, in highly conjugated
porphyrin arrays, the increase of fluorescence quantum yield is due to the
accompanying decrease of triplet state formation, and thus highly conjugated
porphyrin arrays are poor photosensitizers. 178

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