1.1 Porphyrins - Friedrich-Alexander-Universität Erlangen-Nürnberg

1 Introduction
components, the limits concerning the effective depth of tissue penetration due to the non-
optimal optical position and low absorbance of the highest Q-band (λ = 630 nm at
ε = 3500 M -1 ·cm -1 ) and severe side effects due to accumulation in the skin causing high
photosensitivity for up to six weeks after treatment. 61,62c,66
Although the 2 nd generation sensitizers represent far more defined compounds absorbing
more efficiently at higher wavelengths (λ = 650-730 nm at ε ≈ 40.000 M -1 ·cm -1 ) 67 , they are
still far from being ideal. For example, one of the major problems to be tackled remains still
unsolved since the compounds accumulate in tumor cells only because of their changed
metabolism without being able to really recognize them.
To realize an effective targeting, the so-called 3 rd generation sensitizers are being developed.
Such compounds combine a photoactive sensitizer with an antibody moiety providing a tool
to address exclusively to malignant tissue. 68 Thereby different approaches can be followed
as either the sensitizers can be directly attached to the antibody or a conjugate might be
formed in terms of a so-called modular carrier system.
20
dye
antibody
antibody
linker
dye
multiplier
Scheme 16. Approaches to 3 rd generation photosensitizers: direct conjugation of dye and
antibody (left) vs. building up a modular carrier system (right).
Both are considered to have their advantages and disadvantages. On the one hand, the first
approach is easier to be synthetically realized, but one risks to severely influence the
antibody’s properties as for sufficient therapeutic purposes usually more than one sensitizer
has to be attached. Such multiple direct binding could affect the active targeting site or even
might lead to a un- or refolding of the peptide structure causing the loss of activity. On the
other hand, the setup of a modular carrier system is oftentimes laborious due to its far more
complex structure. But it enables the complete preservation of the function of the antibody
and a tunable photoactivity as number and species of the dyes can be varied. Both
approaches are currently under investigation. 68