Reference number : GC-2017-Q1-01459, amendment number : , agreement type : G, recipient legal name : Winnik, Mitchell (University of Toronto), recipient country : CA, recipient province : nan, recipient city : Ontario, recipient postal code : nan, program name english : Discovery Grants Program - Individual, program name french : Programme de subventions à la découverte - individuelles, program purpose english : My research is focused on developing new fundamental scientific knowledge about polymers as materials in areas where one can have an impact on modern technology or medicine. Much of our effort is devoted to the creation and study of polymer objects that form stable colloids in solution, with a uniform well-defined shape and with nanometer or micrometer dimensions. This proposal describes two broad projects, both in the area of polymer materials. One focuses on block copolymer self-assembly in solution. In collaboration with I. Manners (Bristol, UK) we have published seminal papers describing the unprecedented formation of nanofiber micelles in solution. This work has in many ways changed how scientists think about block copolymer micelle formation, particularly when the core-forming polymer is crystalline. In these studies, polyferrocenylsilane (PFS) was the core-forming block. It remains the only type of block copolymer that can form nanowires with a uniform and controllable length. Here I describe new experiments to understand mechanistically why and how such control of self assembly is possible, and how the PFS polymer molecules can fold as they add to the ends of the growing micelles to form crystals of such tiny dimensions. Because the growth of these nanofibers has key features in common with the formation of amyloid fibers associated with human diseases, but without the complications of fragmentation and aggregation, kinetic studies of PFS block copolymer micelle growth could provide important information about factors that affect nanofiber formation in solution. 
 
The other project is based on the idea that we can apply our extensive experience with rod-like colloidal nanostructures to test an idea in the current literature that nanosize rod-like drug delivery vehicles penetrate into tumors more effectively than spherical nanoparticles. We propose to prepare two types of rod-like nanocolloids in water, one based on cellulose nanocrystals and one based on PFS nanowire micelles. We will develop new chemistry to synthesize these nanorod colloids in which we will control the length of the rods, their cross section width, and their surface chemistry. Then, in collaboration with Prof C Allen (Pharmacy), my students will test the ability of these different structures to penetrate multicellular tumor spheroids, known to be good models for solid tumors in vivo , and compare the results with more traditional spherical nanoparticles. While the focus of these studies is entirely mechanistic, the results will have important implications for the application of these materials in nanomedicine., program purpose french : My research is focused on developing new fundamental scientific knowledge about polymers as materials in areas where one can have an impact on modern technology or medicine. Much of our effort is devoted to the creation and study of polymer objects that form stable colloids in solution, with a uniform well-defined shape and with nanometer or micrometer dimensions. This proposal describes two broad projects, both in the area of polymer materials. One focuses on block copolymer self-assembly in solution. In collaboration with I. Manners (Bristol, UK) we have published seminal papers describing the unprecedented formation of nanofiber micelles in solution. This work has in many ways changed how scientists think about block copolymer micelle formation, particularly when the core-forming polymer is crystalline. In these studies, polyferrocenylsilane (PFS) was the core-forming block. It remains the only type of block copolymer that can form nanowires with a uniform and controllable length. Here I describe new experiments to understand mechanistically why and how such control of self assembly is possible, and how the PFS polymer molecules can fold as they add to the ends of the growing micelles to form crystals of such tiny dimensions. Because the growth of these nanofibers has key features in common with the formation of amyloid fibers associated with human diseases, but without the complications of fragmentation and aggregation, kinetic studies of PFS block copolymer micelle growth could provide important information about factors that affect nanofiber formation in solution. 
 
The other project is based on the idea that we can apply our extensive experience with rod-like colloidal nanostructures to test an idea in the current literature that nanosize rod-like drug delivery vehicles penetrate into tumors more effectively than spherical nanoparticles. We propose to prepare two types of rod-like nanocolloids in water, one based on cellulose nanocrystals and one based on PFS nanowire micelles. We will develop new chemistry to synthesize these nanorod colloids in which we will control the length of the rods, their cross section width, and their surface chemistry. Then, in collaboration with Prof C Allen (Pharmacy), my students will test the ability of these different structures to penetrate multicellular tumor spheroids, known to be good models for solid tumors in vivo , and compare the results with more traditional spherical nanoparticles. While the focus of these studies is entirely mechanistic, the results will have important implications for the application of these materials in nanomedicine., agreement title english : Polymer Conformation, Dynamics, Morphology, agreement title french : Polymer Conformation, Dynamics, Morphology, agreement number : RGPIN, agreement value : 620000.0, agreement start date : 2017-05-10, agreement end date : nan, description english : nan, description french : nan, expected results english : nan, expected results french : nan, additional information english : Grant or Award spanning more than one fiscal year. (2017-2018 to 2022-2023), additional information french : Subvention ou bourse octroyée s'appliquant à plus d'un exercice financier. (2017-2018 à 2022-2023), owner organization : nserc-crsng, owner organization title : Natural Sciences and Engineering Research Council of Canada | Conseil de recherches en sciences naturelles et en génie du Canada