Multifunctional Nanomaterials For Cancer Therapy

Cancer,also known as malignant tumors,has become the second leading cause of death globally,seriously endangering human health.Designing multifunctional nanoprobes based on unique chemical and physical properties of nanomaterials has become a hot topic for cancer therapy.In this dissertation,we developed several on-demand nanomaterials for targeted drug delivery and synergistic therapy.The main contents are as follows:1.Acid-responsive nanoscale coordination polymers for chemotherapy and magnetic resonance imagingConsidering the pH differences in tumor tissues,we designed an Gd-based nanoscale coordination polymers(GdNCP)for targeted drug delivery and magnetic resonance imaging.The prepared GdNCP is stable in neutral environment but will quickly breaks into fragments in acid environment.Dox is loaded into GdNCP by coordination with Gd3+,which quenches its inherent fluorescence.The surface immobilization of hyaluronic acid onto the NCP not only inhibits premature drug release,but also acts as a targeting ligand towards the overexpressed CD44 of cancer cells.After internalization into HeLa cells,the nanoprobes are rapidly dissolved in the acidic intracellular compartments,and as a result,the loaded drug and metal ion Gd3+are released into the cytosol.The recovered fluorescence of Dox allows real-time monitoring of drug release and the broken piece of GdNCP enhances T1-weighted magnetic resonance signals.Such nanomaterials have excellent biocompatibility,biodegradability and targeting capacity,showing great promise for cancer therapy.2.In situ synthesis of MnO2 into the large pore of silica for improved photodynamic therapy in hypoxic environment and T1-weighted MRI.The low selectivity of traditional photosensitizer and the hypoxic environment in tumor tissues often restrict the clinical application of photodynamic therapy.Given these,we use large pore silica as substrates,into which in situ synthesis of MnO2 is achieved.The prepared silica-MnO2 nanocomposites are applied to covalently load photosensitizers followed by decoration with aptamers,exhibiting a quick response to H+/H2O2.After internalization into HeLa cells,the high reactivity of MnO2 towards endogenous H+/H2O2 leads to simultaneous generation of O2 and Mn2+.The massive O2 improves the efficiency of photodynamic therapy,while Mn2+ reacts as T1-weighted MRI contrast.Such O2-evolving and H+/H2O2-activatable nanomaterials with good biocompatibility show great potentials in clinic application.3.NIR-triggered drug delivery and photodynamic therapy by UCNPs@MOF structures.Due to prominently deeper tissue penetration and much less damage to living tissues,near-infrared irradiation has been widely explored in biomedical application.We develop a new strategy for epitaxial growth of metal organic frameworks(MOF)onto upconversion nanoparticles(UCNPs)in order to realize NIR-triggered drug delivery and photodynamic therapy.Upon exposure to 980 nm light,the multilayered UCNPs will emit photons in the UV/Vis region,which can be absorbed by the photoresponsive azo group and photosensitizers inserted in the MOF.Photoisomerization of azo group upon UV/vis lights leads to the release of anti-cancer drugs,in the meanwhile,photosensitizers under visible light exposure will create toxic 1O2.By exploring such newly developed nanostructures,we may achieve NIR-triggered drug delivery and photodynamic therapy in the same time.