SUNY at Albany
June 19-23, 2001
Chiral Self-Assemblies of Hematoporphyrin IX Derivatives in Tissue
Self-assembly of the chiral porphyrin molecules HpD (3,3´- [7,12-bis(1-aceto(oxyethyl)-3,8,13,17-tetramethyl-21H,23H- porphyrin-2,18-diyl]-bispropionic acid, hematoporphyrin IX derivative) is shown to form helical fibers in low salted aqueous conditions (see Fig. 1). The properties of HpD (used in medicinal therapies as Photosan II) were investigated spectroscopically (UV and CD), and microscopically (light and scanning force microscopy) in the presence of nucleic acid double strands. The asymmetric HpD molecules themselves show at room temperature sharp positive or negative CD signals, which increase enormously with drug. The data show strong evidence for external self-stacking interaction of HpD, pure and in the presence of polynucleotides.
Figure 1:(top) SFM observation of chiral HpD self-assemblies, (bottom) scheme of porphyrin self-assembly with chiral aspects.
Additionally in the present study, cells from human head-neck squamous cell carcinoma (hypopharynx, UMSCC11 and UMSCC22) and lung tumor (alveolus, UMSCC7) were investigated by light and scanning force microscopy (SFM) observation. Most of the drug treated head-neck tumor cells died (only 2-5 % of survivors). The damage and cell death could partly be visualized by observing the hypopharynx tumor cells incubated with HpD. Already after a few minutes (30 min) a distortion of the cell and its membrane under drug influence becomes visible. After three days in the shattered tissues (cell lines UMSCC11 and 22) three-dimensional chiral associations induced by the drug were observed (spirals and helices, see Fig. 2).
Figure 2: SFM observation of degenerated tissue 3 days after HpD treatment.
However, HpD could not affect cells of the lung tumor cell type. They, well known as more resistant against oxidation processes, survived to a great extent. Also, no distortion of the membrane under drug treatment could be observed. In conclusion, the spiral-like superstructures of the HpD self- assemblies themselves and in the presence of nucleic acid or tissues are important phenomena for the comprehension of biomolecular reactions. In particular, because of the presence of porphyrins is absolutely indispensable for biological occurrences.
Robert Bischoff (1), Gerlinde Bischoff (2), Siegfried Hoffmann (2)
Martin Luther University (2), Halle-Wittenberg, Department of Biochemistry/Biotechnology,