Photochemical internalization of bleomycin for glioma treatment.

We study the use of photochemical internalization (PCI) for enhancing chemotherapeutic response to malignant glioma cells in vitro. Two models are studied: monolayers consisting of F98 rat glioma cells and human glioma spheroids established from biopsy-derived glioma cells. In both cases, the cytotoxicity of aluminum phthalocyanine disulfonate (AlPcS2a)-based PCI of bleomycin was compared to AlPcS(2a)-photodynamic therapy (PDT) and chemotherapy alone. Monolayers and spheroids were incubated with AlPcS(2a) (PDT effect), bleomycin (chemotherapy effect), or AlPcS(2a)+bleomycin (PCI effect) and were illuminated (670 nm). Toxicity was evaluated using colony formation assays or spheroid growth kinetics. F98 cells in monolayer/spheroids were not particularly sensitive to the effects of low radiant exposure (1.5 J/cm(2) @ 5 mW/cm(2)) AlPcS(2a)-PDT. Bleomycin was moderately toxic to F98 cells in monolayer at relatively low concentrations-incubation of F98 cells in 0.1 µg/ml for 4 h resulted in 80% survival, but less toxic in human glioma spheroids respectively. In both in vitro systems investigated, a significant PCI effect is seen. PCI using 1.5 J/cm(2) together with 0.25 µg/ml bleomycin resulted in approximately 20% and 18% survival of F98 rat glioma cells and human glioma spheroids, respectively. These results show that AlPcS(2a)-mediated PCI can be used to enhance the efficacy of chemotherapeutic agents such as bleomycin in malignant gliomas.

Thermodynamic and structural characterization of amino acid-linked dialkyl lipids.

Using differential scanning calorimetry (DSC), X-ray diffraction (XRD) and Fourier transform infrared spectroscopy (FTIR), we determined some thermodynamic and structural parameters for a series of amino acid-linked dialkyl lipids containing a glutamic acid-succinate headgroup and di-alkyl chains: C12, C14, C16 and C18 in CHES buffer, pH 10. Upon heating, DSC shows that the C12, C14 and annealed C16 lipids undergo a single transition which XRD shows is from a lamellar, chain ordered subgel phase to a fluid phase. This single transition splits into two transitions for C18, and FTIR shows that the upper main transition is predominantly the melting of the hydrocarbon chains whereas the lower transition involves changes in the headgroup ordering as well as changes in the lateral packing of the chains. For short incubation times at low temperature, the C16 lipid appears to behave like the C18 lipid, but appropriate annealing at low temperatures indicates that its true equilibrium behavior is like the shorter chain lipids. XRD shows that the C12 lipid readily converts into a highly ordered subgel phase upon cooling and suggests a model with untilted, interdigitated chains and an area of 77.2A(2)/4 chains, with a distorted orthorhombic unit subcell, a=9.0A, b=4.3A and beta=92.7 degrees . As the chain length n increases, subgel formation is slowed, but untilted, interdigitated chains prevail.