Functionalized PISA particles for targeted delivery and imaging

Abstract

Polymer based nanoparticles are widely used in various biomedical applications due to their easily tunable size and morphology. Furthermore, characteristic properties such as solubility or biocompatibility can also be adapted depending on the needs of the application. Desired properties can easily be incorporated with the right choice of material from an extensive pool of available polymers Micellar structures are one of the most utilized examples of polymeric nano-structures with their amphiphilic nature, controllable size, morphology and surface properties on top of their unique capability of encapsulating host molecules. They can be obtained effortlessly with a one pot, straightforward reaction, by using polymerization induced self-assembly (PISA) technique. In this study, our aim is to obtain micellar polymeric nanomaterial with a functionalizable surface and guest molecule encapsulation capability by using the PISA technique. Surface functionalizability will be used to introduce targeting units on the surface of the nanoparticles for specific cancer tissues, whereas the hosting through encapsulation will be used to carry hydrophobic dyes as cargo. For this purpose, p(PEGMEMA)-b-pST copolymers with dibromomaleimide (DBM) end groups were synthesized in a solvent, where they will self-assemble during the polymerization of the second block and form stable nanomaterial. It was observed that the formation of the nanoparticles were dependent on the degree of polymerization of the solvophobic pST block. Nile red, a hydrophobic dye, was also introduced in the media during the polymerization and encapsulated by the nanoparticles in situ. The DBM moieties on the surface were used for further functionalization of the particles as they are well known to give fast and mild reactions with free thiol-containing compounds. Nanoparticles were reacted with two different thiol bearing molecules, one of which was a cysteine containing peptide that has very high affinity for integrin receptors that are overexpressed on cancer tissues. Consequently, a new type of surface functionalized PISA particles with targeting property and guest molecule encapsulation capability are successfully synthesized.