Biophysical interaction of temozolomide and its active metabolite with biomembrane models: The relevance of drug-membrane interaction for Glioblastoma Multiforme therapy.

Temozolomide (TMZ) is the first-line treatment for Glioblastoma Multiforme (GBM). After administration, TMZ is rapidly converted into its active metabolite (MTIC). However, its pharmacological activity is reduced due MTIC low bioavailability in the brain. Since drugs' permeability through biological barriers and tumor cell membranes affects its bioavailability, the ability of MTIC to interact with the biological membranes presents a major contribution on its pharmacological properties and activity. Biomembrane models mimic the physiological conditions, allowing to predict the drug's behavior at biological membranes and its effects on drug biodistribution profiles. In this work, lipid bilayer models using liposomes were applied for the drug-membrane interaction studies. The zwitterionic phospholipid, 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC), and cholesterol were chosen for the composition of the model, since they represent the major components of the membranes of GBM cells and brain capillary endothelial cell. Thus, the molecular interactions between MTIC and these models were studied by the evaluation of the partition of the drug into the phospholipid's membrane, its location within the bilayer and its effect on the fluidity of the membrane. The attained results suggest that the composition of membranes affects drugs partition, showing that drug biodistribution depends not only on its physicochemical features, but also depends on the characteristics of the membrane such as the packing of the lipid molecules. Also, MTIC exhibited low affinity to biological membranes, explaining its low bioavailability on the target cells.

Quantum dots and nanoparticles for photodynamic and radiation therapies of cancer.

Semiconductor quantum dots and nanoparticles composed of metals, lipids or polymers have emerged with promising applications for early detection and therapy of cancer. Quantum dots with unique optical properties are commonly composed of cadmium contained semiconductors. Cadmium is potentially hazardous, and toxicity of such quantum dots to living cells, and humans, is not yet systematically investigated. Therefore, search for less toxic materials with similar targeting and optical properties is of further interest. Whereas, the investigation of luminescence nanoparticles as light sources for cancer therapy is very interesting. Despite advances in neurosurgery and radiotherapy the prognosis for patients with malignant gliomas has changed little for the last decades. Cancer treatment requires high accuracy in delivering ionizing radiation to reduce toxicity to surrounding tissues. Recently some research has been focused in developing photosensitizing quantum dots for production of radicals upon absorption of visible light. In spite of the fact that visible light is safe, this approach is suitable to treat only superficial tumours. Ionizing radiation (X-rays and gamma rays) penetrate much deeper thus offering a big advantage in treating patients with tumours in internal organs. Such concept of using quantum dots and nanoparticles to yield electrons and radicals in photodynamic and radiation therapies as well their combination is reviewed in this article.

Stable polymethacrylate nanocapsules from ultraviolet light-induced template radical polymerization of unilamellar liposomes.

We employed UV-induced template polymerization to create hollow nanometer-sized polymer capsules. Homogeneous, unilamellar liposomes served as a two-dimensional template for the cross-linking of either butyl methacrylate or hydroxyethyl methacrylate with the bifunctional ethyleneglycol dimethacrylate. Different molar ratios of lipid/hydrophobic monomer/bifunctional monomer/photoinitiator were tested and dynamic light scattering revealed negligible changes of size at a defined molar ratio of 2/1/10/20, respectively. Cryo-transmission electron microscopy provided clear evidence that incorporation of the methacrylate monomers into and polymerization in the hydrophobic bilayer phase does not disrupt vesicle integrity. Moreover, after solubilization of the lipids, the polymethacrylate nanocapsules were stable at conditions needed for negative staining and could be visualized by atomic force microscopy. In contrast to previous findings, the nanocapsule size and shape did not change considerably after removal of the template phase, and the size distribution remained strictly monomodal. The employed method is not only an advance to fortify liposomes, but the nanocapsules themselves can be functionalized.