Preparation Of Polyglycine Functionalized Inorganic Nanoparticles And Its Application For Cancer Therapy

Polyglycerol?PG?fictionalization had been reported that PG layer can be functionalized on the inorganic nanoparticles surface by ring-opening polymerization of glycidol.In this dissertation,polyglycerol?PG?fictionalization was used as the surface modification method to enhance biomedical applications of several inorganic nanoparticles.The surface of nanoparticles grafted by PG have a lot of hydroxyl terminal groups,which can increase the dispersibility and stability of nanoparticles in aqueous solutions.Moreover,some reactive functional groups such as amino groups and carboxyl groups can be grafted by PG layer through various chemical modification and organic transformations.These groups can be further modified with other functional groups to form a large number of functional moieties such as targeting ligands and anticancer drugs.In addition,PG layer also has other special biological effect such as preventing non-specific cell uptake and avoiding the capture by the reticuloendothelial system.1.Preparation of polyglycine functionalized manganese oxide?MnO?nanoparticles and its application for chemotherapy of cancer therapyMnO nanoclusters were prepared by polyol method and grafted with polyglycerol?MnO-PG?.Then,MnO-PGwasconjugatedwith arginine-glycine-aspartate peptide through stepwise organic reactions?MnO-PG-RGD?.The PG layer not only enhanced the dispersibility and colloidal stability of MnO nanoclusters in aqueous solutions,but also inhibited cellular uptake of MnO-PG.In contrast,MnO-PG-RGD nanoparticles were selectively taken up by human glioblastoma U87MG cells,which overexpressing?_v?₃ integrins.The internalized MnO-PG-RGD was mainly located in the lysosomes of U87MG cells.The acidity of lysosome accelerated Mn²⁺ions releasing,which promoted intracellular oxidative stress further leading to cell damage and apoptosis.The results indicate that approporate surface functionalization can enable MnO nanoparticles to act as a potential anticancer agent in addition to their MRI functionality.2.Preparation of polyglycine functionalized zinc oxide?ZnO?nanoparticles and its application for chemotherapy of cancer therapyRed fluorescence ZnO nanoparticles were synthesized,grafted with polyglycerol to form ZnO-PG and conjugated with RGD peptide to form ZnO-PG-RGD by stepwise organic reactions.Anticancer drugs DOX were immobilized on ZnO-PG-RGD to form ZnO-PG-RGD/DOX by n-?conjugated stack.The ZnO-PG not only increases the dispersibility in a physiological environment,but also release anticancer drugs in an acid-responsive.The results of the cell experiments indicated that PG layer hided ZnO nanoparticles from the uptake by U87MG.In contrast,ZnO-PG-RGD was selectively taken up by U87MG cells,demonstrating obvious targeting property.When ZnO-PG-RGD/DOX was used,U87MG cells showed specificity cytotoxicity.Therefore,functionalized ZnO nanoparticle was a promising nanomaterial in cancer theranostics.3.Preparation of polyglycine functionalized magnetic mesoporous silica nanohybrid and its application for photodynamic of cancer therapyA versatile strategy based on polyglycerol mediated covalent linkage was developed to fabricate a core-satellite nanocompose,named MMSN,which consisting of a mesoporous silica nanoparticle?MSN?as a core and many superparamagnetic iron oxide nanoparticles?SPION?on the outer surface.Thanks to the firm amide linkage,no obvious Ce6 release was detected when Ce6@MMSN was dispersed in acidic to weak basic solutions.Taking advantage of the combined porosity and magnetic property of the nanohybrid,a photosensitizer chlorin e6?Ce6?is loaded on MMSN and efficiently delivered into target cells under magnetic guidance,leading to an enhanced efficacy of photodynamic therapy?PDT?.