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
Even though great progress has been made in the understanding of fundamental cancer biology and cancer therapy, the translation from fundamental research to advances in clinic is yet to be better addressed. One of the major issues is to selectively deliver the therapeutic cargos to the desired target so that collateral damage can be minimized. The project “A Versatile Platform for the Design of Targeting Drug Delivery Vesicles”, abbreviated “VesSenDrugDeliv”, was to discover a versatile molecular platform that can be used to co-assemble with various functional moieties in aqueous solution to prepare efficient targeting drug delivery nanoparticles. By doing so, we aimed to use this type of nanoparticles to increase the targeting selectivity and enhance the therapeutic efficacy toward targeted tumour cells.
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.
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.
Final Results Overview:
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.
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.
"Even though there are a large number of publications and patents about cancer treatment with targeting drug delivery nanoparticles, the multifunctionalisation of these nanoparticles requires complicated synthesis and sophisticated skills. Besides, it is not trivial to make them monodisperse and their size suitable for drug delivery. In the “VesSenDrugDeliv” project, we conceived a new and simple type of multifunctional targeting drug delivery nanoparticles that were co-assembled by multifunctional amphiphiles and conjugated polymer F8BT. The multifunctionalisation has been achieved by easily tuning the chemical structure of the multifunctional amphiphiles. Besides, the preparation of the 100 nm-sized monodisperse particles was simply achieved by injecting the ethanol solution of the mixture of multifunctional amphiphiles and F8BT into water or various buffers. By programming the density of the targeting ligand folate, we revealed that the ligand density had an important impact on the internalization ability of the nanoparticles into cancer cells. This new type of nanoparticles could potentially be used for targeting, imaging and treatment of tumors at the same time. The knowledge gained from this project will be very beneficial for the further development of innovative cancer treatment.
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).
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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).
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