Therapeutic Effects of AICAR and DOX Conjugated Multifunctional Nanoparticles in Sensitization and Elimination of Cancer Cells via Survivin Targeting

WOS: 000391431900015PubMed ID: 27783307Resistance to chemotherapy is one of the major problems facing current cancer research. Enhancing tumor cell response to anticancer agents increases chemotherapeutic effectiveness. We have recently addressed this issue and reported on producing multifunctional nanoparticles (Fe3O4@SiO2(FITC)-FA/AICAR/DOX) aiming to overcome chemoresistance with synergetic effect of AICAR and DOX. In the present study, we demonstrated that these nanoparticles not only show enhanced cellular uptake and cytotoxic effect but can also show enhanced pro-apoptotic and anti-proliferative effects in five different tumor-derived cell lines (A549, HCT-116, HeLa, Jurkat and MIA PaCa-2). The nanoparticles were examined by using flow cytometric analyses of apoptosis and cell cycle. In addition, we performed caspase-3 activity assay, which supported our flow cytometric data. Furthermore, we demonstrated the applicability of this approach in a variety of cancer types confirming the potential widespread utility of this approach. With the concept of co-delivery of AICAR and DOX in the nanoparticle formulation, the use of AICAR against survivin (BIRC5) sensitized cancer cells to DOX chemotherapy which resulted in effective cancer cell elimination. These result showed that combination therapy involving both a molecularly targeted therapy and chemotherapeutic agent has the ability to retain and enhance therapeutic efficacy. Fe3O4@SiO2(FITC)-FA/AICAR/DOX nanoparticles is superior to monotherapy via the synergetic effect of AICAR and DOX and also the nanoparticle formulation could overcome issues of toxicity with targeted therapy while maintaining the potent anticancer effects of AICAR and DOX

Covalent immobilization of trypsin on glutaraldehyde-activated silica for protein fragmentation

WOS: 000311817900003PubMed ID: 22670793Trypsin was immobilized by covalent binding to glutaraldehyde-activated silica with and without a spacer arm; 1,6-diaminohexane and polyethyleneglycol as well. The addition of polyethyleneglycol (PEG) to the immobilization media increased the activity of immobilized trypsin in organic solvents, whilst free trypsin activity disappeared under the same conditions. Thermal, pH, storage, and operational stabilities of the free and immobilized enzyme were found to be better than the free enzyme. Furthermore, use of immobilized enzyme for protein fragmentation was achieved by solid-phase, on-line, protein digestion in organic solvents. Reaction times were reduced to a few minutes and the sample handling was minimized.Scientific Research Foundation of Ege University, Izmir, Turkey (BAP)Ege University [Sci-2010 - 003]The authors would like to thank Professor U.T. Bornscheuer (University of Greifswald) for providing the opportunity to work in his laboratory during part of this study. This work was partially supported by the Scientific Research Foundation of Ege University, Izmir, Turkey (BAP-Grant Number Sci-2010 - 003)

Synthesis and Characterization of AICAR and DOX Conjugated Multifunctional Nanoparticles as a Platform for Synergistic Inhibition of Cancer Cell Growth

WOS: 000374812600028PubMed ID: 26996194The success of cancer treatment depends on the response to chemotherapeutic agents. However, malignancies often acquire resistance to drugs if they are used frequently. Combination therapy involving both a chemotherapeutic agent and molecularly targeted therapy may have the ability to retain and enhance therapeutic efficacy. Here, we addressed this issue by examining the efficacy of a novel therapeutic strategy that combines AICAR and DOX within a multifunctional platform. In this context, we reported the bottom-up synthesis of Fe3O4@SiO2(FITC)-FA/AICAR/DOX multifunctional nanoparticles aiming to neutralize survivin (BIRC5) to potentiate the efficacy of DOX against chemoresistance. The structure of nanoparticles was characterized by dynamic light scattering (DLS), zeta-potential measurement, X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FT-IR), thermogravimetric analysis (TGA), and electron microscopy (SEM and STEM with EDX) techniques. Cellular uptake and cytotoxicity experiments demonstrated preferentially targeted delivery of nanoparticles and an efficient reduction of cancer cell viability in five different tumor-derived cell lines (A549, HCT-116, HeLa, Jurkat, and MIA PaCa-2). These results indicate that the multifunctional nanoparticle system possesses high inhibitory drug association and sustained cytotoxic effect with good biocompatibility. This novel approach which combines AICAR and DOX within a single platform might be promising as an antitumor treatment for cancer