Surface Modification Of Functional Nanomaterials Applied In Bio-imaging And Drug Delivery

With the great advancement of nanotechnology, various functional nanomaterials have found great applications in biomedical fields while certain challenges remain. To get inorganic nanomaterials with improved performance, inorganic nanocrystals capped with hydrophobic ligands were mostly synthesized in organic solvents with high boiling points. To apply these nanomaterials with diverse properties to biomedical fields, such as bio-imaging and drug delivery, hydrophilic nanomaterials are in great demands. In this thesis, we focused on synthesis of hydrophilic nanoparticles, surface modification of hydrophobic nanomaterials and their bio-applications including cell imaging, in vivo drugs tracking and controlled drug release as following:By using water as an exclusive solvent, a facile one-pot strategy was developed for the preparation of hydrophilic magnetite nanofluids coated with oxidized dextran. These as-synthesized magnetic nanofluids are highly water-soluble, biocompatible, and bioconjugatible for targeted detection because of the enriched carboxylate groups in the oxidized dextran shell. These nanoparticles are less than 10 nm and demonstrate strong magnetization, low cytotoxicity, and high T2-weighted MR image signal intensity (r2= 250.5 mM-1s-1,3.7 times largerthan the commercial product). These novel properties render this magnetic nanofluid desirable for wide bioapplications including MRI, highly efficient magnetic bioseparation, targeted drug delivery, and magnetic hyperthermia.Hydrophobic nanocrystals with various shape, size, and chemical composition were successfully functionalized by poly(amino acid) with one particle per micelle without aggregation or precipitation via a facile, general, and low-cost strategy.Via simply tuning the pH value, multifunctional nanocomposites consisting of different nanocrystals were also fabricated. Due to the poly(amino acid) coating, these nanocrystals are highly water-stable, biocompatible, and bioconjugatable with chemical and biological moieties. Meanwhile, their shape, size, optical/magnetic properties are well retained, which is highly desirable for bioapplications. This developed strategy presents a novel opportunity to apply hydrophobic nanocrystals to various biomedical fields.Nanocapsule-based targeted delivery and stimuli-responsive release can increase drug effectiveness while reducing side effects. However, difficulties in the scaling-up synthesis, fast burst release, and low degradability are likely to hamper the translation of drug nanocapsules from lab to clinic. Here we controllably functionalize the biodegradable and widely available polysuccinimide to get the amphiphilic poly(amino acid). By using this polymer, we design the nanocapsules (<100 nm) for hydrophobic drug delivery that can provide tumor targeting, hydrogen-bond-based pH-responsive release, and real-time fluorescence tracking in the second near-infrared region. This method is versatile, green, and easy to scale up at low cost for cocktail drug by loading multiple anticancer drugs. Our nanocapsules are stable in blood vessel (pH 7.4) and the pH-responsive release (pH 5.0 in lysosome) is sustained. The chemotherapy results in tumor xenografted mice suggest that our nanocapsule is safe and efficient and may be a useful tool for drug delivery.Thermosensitive drug delivery systems (DDSs) face great challenging in remote and repeatable control of in vivo temperature despite they can overcome many hurdles of conventional DDSs in order to increase therapeutic efficacies. We address this issue by coating near-infrared (NIR) photothermal Gu1.75S nanoparticles with pH/thermo sensitive polymer via in-situ polymerization. The doxorubicine (DOX) loading content can be up to 40 wt%, and less than 8.2 wt% of DOX was leaked under normal physiological condition (pH 7.4,37℃) within 48 h at the absence of NIR light, suggesting it is suitable for drug delivery. These nanocapsules demonstrate excellent photothermal stability via continuous long-term NIR irradiation up to several hours. Based on the stable and ultrahigh NIR photothermal efficiency (74.6%) of Gu1.75S NPs, the pre-loaded drugs can be released as desired by using NIR (808 nm) light as a trigger. Both in vitro and in vivo antitumor therapy results suggest this smart nanoplatform is an effective agent for synergetic hyperthermia-chemotherapy of cancer with remote and noninvasive control.