Testing the photo-sensitive nanocomposite system for potential controlled metallo-drug delivery

Photo-responsive drug release systems are promising for drug delivery applications due to many benefits compared to conventional chemotherapy such as targeted, controlled release of a drug and reduced toxicity to healthy tissues. In this work, we report synthesis of the nanocomposite system based on carrier TiO2 nanoparticles and potential anticancer ruthenium complex, with light controllable release properties. Nanocomposite system showed biological activity and induced the generation of free radicals, which are implied in the efficient cell killing. The drug release tests demonstrated sustained release of the transition metal complex from the surface implying the potency for the controlled drug delivery system. Taking into account photoactivity of the Ru-complex, in the next step we have investigated the influence of green light on the rate of the complex release, and the results showed dependence of the Ru-complex release from the surface of TiO2 nanoparticles on the applied laser energy. Therefore, these characteristics make this nanocomposite system promising for the photo-responsive chemotherapy

Computational study and peptide inhibitors design for the CDK9 – cyclin T1 complex

Cyclin dependent kinase 9 (CDK9) is a protein that belongs to the cyclin-dependent kinases family, and its main role is in the regulation of the cell transcription processes. Since the increased activity of CDK9 is connected with the development of pathological processes such as tumor growth and survival and HIV-1 replication, inhibition of the CDK9 could be of particular interest for treating such diseases. The activation of CDK9 is initiated by the formation of CDK9/cyclin T1 complex, therefore disruption of its formation could be a promising strategy for the design of CDK9 inhibitors. In order to assist in the design of potential inhibitors of CDK9/cyclin T1 complex formation, a computational study of the CDK9/cyclin T1 interface was conducted. Ten peptides were designed using the information from the analysis of the complex, hot spot residues and fragment based design. The designed peptides were docked to CDK9 structures obtained by molecular dynamics simulations of CDK9/cyclin T1 complex and the CDK9 alone and their binding affinities were evaluated using molecular mechanics Poisson Boltzman surface area (MM-PBSA) method and steered molecular dynamics (SMD). Designed peptide sequences LQTLGF and ESIILQ, both derived from the surface of cyclin T1, as well as the peptide sequence PRWPE, derived from fragment based design, showed the most favorable binding properties and were selected for our further studies