Project description:Nanoparticles exposed to biological fluids are rapidly surrounded by proteins. It is known that this formed protein corona influences the interplay of nanoparticles with cells or tissue barriers. In this study, we report the impact of a formed human plasma protein corona on the transfer of 80 nm polystyrene (PS) nanoparticles across the human placenta. We used the human ex-vivo placental perfusion model, as it reflects the intact and physiological tissue barrier between mother and unborn. Our results show an enhanced transfer of polystyrenes, exposed to human plasma, across the placenta compared to bovine serum albumin which served as control setting. We isolated nanoparticles before and after tissue exposure and analyzed their protein corona via shotgun proteomics and LC-MS/MS. The corona profile of particles that crossed the placenta highlighted several proteins as possible drivers for elevated tissue transfer. Subsequently two distinct proteins, human albumin and immunoglobulin G, were selected and incubated with the nanoparticles to form a sole protein corona. Strikingly, the protein corona formed by albumin induced significantly the transfer of polystyrenes across the tissue as compared to corona formed by immunoglobulins. To conclude, our study provides a comparative analysis between different formed protein coronas on nanoparticles and a corona dependent transfer behavior of polystyrenes across placental tissue. Our findings suggest that protein corona analyses of nanoparticles might help to understand better their properties at biological barriers.
Project description:Cisplatin is a widely used anti-tumor agent for the treatment of testicular and ovarian cancers. Carboplatin is used extensively for small cell, non small cell lung cancer and ovarian cancer. Oxaliplatin has recently been approved in the United States (US) for treatment of colorectal cancer. A large portion (in the range of 65% to 98%) of cisplatin in the blood plasma was bound to protein within a day after intravenous administration. The binding of cisplatin and other analogues to proteins and enzymes is generally believed to be the cause of several severe side effects such as ototoxicity and nephrotoxicity. The interactions between platinum based chemotherapy drugs and proteins is proposed to play important roles in both drug activity and toxicity. Therefore, a better understanding of the molecular mechanism of platinum-protein interactions may have an impact on optimization of strategies for treatment. The objective is to develop novel approaches and techniques to provide detailed mechanistic, kinetic and high-resolution structural information on the binding of platinum analogues to blood proteins, and to improve treatment efficacy and reduce side effects.