Determinants of photosensitization by purpurins.

Studies were carried out on two purpurins, NT2 and an analog, Sn.NT2H2. Both are photosensitizers, but the latter is substantially more effective against neoplastic cells in vivo. These hydrophobic dyes can be solubilized via Cremophor EL emulsions. We found both dyes to be approximately equitoxic to murine leukemia L1210 cells in culture, in terms of intracellular concentrations. But uptake of NT2 was 10-fold less efficient than Sn.NT2H2, i.e. a 10-fold higher extracellular level of NT2 was needed to produce an equitoxic response. Fluorescence measurements indicate that NT2 partitions to a very hydrophobic intracellular environments; its phototoxicity was related to inhibition of biosynthesis of DNA. In contrast, SN.NT2H2 was accumulated at more hydrophilic loci (the apparent dielectric constant is consistent with a membrane interface) and mediated photodamage at sites of membrane transport.