Periodic Reporting for period 1 - VesSenDrugDeliv (A versatile platform for the design of targeting drug delivery vesicles)
Reporting period: 2015-07-01 to 2017-06-30
Significant transfer of knowledge was involved during my stay at Imperial College London sponsored by this MSCA-IF fellowship. This includes the training acquired in using the-state-of-the-art facility such as transmission electron microscope (TEM), scanning electron microscope (SEM) and circular dichroism (CD). There were great opportunities of building-up worldwide collaboration with top scientists from UK, France and Australia. I was also able to develop invaluable supervision and management skills when mentoring master and Ph.D. students with different background. Moreover, the multinational culture and multidisciplinary environment at the Stevens Group at has fully supported the multidisciplinary “VesSenDrugDeliv” project.
During the “VesSenDrugDeliv” project we have been successful in developing a versatile molecular platform that can be used to co-assemble with the conjugated polymer F8BT. The versatile molecular platform is a type of pyrene-containing multifunctional amphiphiles, of which the pyrene moiety was used as the FRET donor. When mixed with F8BT as the FRET acceptor in aqueous solution, the two counterparts formed monodisperse nanoparticles via non-covalent π-π stacking. High fluorescence enhancement via efficient energy transfer from multifunctional amphiphiles to F8BT was determined by fluorometry. Further functionalisation of the versatile molecular platform with targeting ligands and prodrugs were also successfully realised. For example, when coupled with folate, the multifunctional amphiphiles can co-assemble with F8BT to form stable and monodisperse nanoparticles that can be used to target the cancer cells with over-expressed folate receptors. By varying the density of folate, we systematically studied the internalization ability of our targeting delivery nanoparticles with different cancer cell lines (MDA-MB-231, MDA-MB-468, MCF-7, and T47F). It showed that the density of the folate had an important impact on the internalization ability of the nanoparticles into the target cells.
Meanwhile, with the support of this MSCA-IF fellowship I was able to broaden my research on the fundamental understanding of amplification of homochirality. We have successfully developed a series of chiral and achiral amphiphiles which self-assemble into supramolecular polymers in water. By using a combination of CD, isothermal titration calorimetry (ITC), nuclear magnetic resonance (NMR) and all-atom simulation, we were able, for the first time, to distinguish the different mechanisms of the extra-dynamic supramolecular polymerisations of chiral and achiral monomers. Importantly, when mixing chiral molecules with achiral ones, we demonstrated that the pure handedness of the achiral molecules was induced by their chiral counterparts, which resulted into the amplification of homochirality.
On the personal level, I was able to conduct the cutting-edge research and build up worldwide collaboration during my stay at Imperial College London. I also obtained very important experience of student supervision, which will be very helpful for my independent career. Thanks to the research experience brought by this MSCA-IF fellowship I have secured the tenure-track assistant professorship (associate professor in China) in Shanghai Jiao Tong University, a prestigious university in my native country China (#62 in QS world university rankings).