Preparation And Drug - Loading Of Rare - Earth Conversion Luminescent Nanomaterials With Novel Structure

In recent years, the design and fabrication of novel drug delivery system have attracted considerable attention. The major goal is to establish a nanomedical platform that controls drug release for reducing the side effects and improving the drug bioavailability. A perfect drug delivery system should integrate individual function with different properties into a single nanocarrier that would simultaneously perform targeted drug delivery and release, diagnosis and therapy, and fluorescent bioimaging to enhance the therapeutic effect and trace drug. Due to the unique upconversion mechanism, the lanthanides based upconversion luminescent materials possess many attractive merits including high detection sensitivity and signal-to-noise ratio, excellent chemical and photostability, greater tissue penetration, absence of photodamage to live organisms, weak autofluorescence background. Therefore, UCNPs have quickly become to be a research hotspot in biological imaging, disease diagnosis， biological sensing/detection and other fields. However, the application in drug delivery is still in the beginning stages. The universal problem is that the study is not systemic, whether in materials structure, controlled synthesis, surface modification or in drug loading and releasing properties.In this dissertation, we designed and synthesized several multi-functional nanocomposites with novel structures. The obtained multi-functional nanocomposites were carefully characteristiced by XRD, SEM, TEM, BET, FTIR, upconversion fluorescence spectrum and other characterization methods. In addition, all the composites were employed as drug carries, and the drug loading and releasing properties were measured by UV-vis absorption spectroscopy. The biocompatibilities were evaluated by MTT proliferation assay and hemolysis assay. This dissertation consists of following five chapters:Chapter 1:The current state of cancer therapy and pathophysiology of tumor cells were briefly introduced firstly. The recent advances in synthesis, surface modification and biomedical applications of UCNPs were then reviewed. And the academic debate and unresolved issues in current research were discussed. The above summary would provide a solid theoretical foundation and scientific basis for the design and synthesis of the multifunctional drug carrier.Chapter 2:We demonstrated a novel, template-free, and one-step method to fabricate a hollow mesoporous structure upconversion luminescent NaYF4:Yb,Er nanoparticles (NaYF4:Yb,Er HMUCNPs) with controllable size and good water dispersion by a simple hydrothermal route. The effects of various reaction conditions on the morphology and size of the as-prepared samples were investigated in detail and Ostwald ripening effect was adapted to explain the formation mechanism of the HMUCNPs. The anti-cancer drug doxorubicin hydrochloride (DOX) storage/release properties were demonstrated to be pH-responsive, in which, the DOX encapsulation efficiency (EE,%) and drug loading content (DLC,%) could up to 62.2% and 15.5% at pH7.4， respectively. However, the drug release might be beneficial at the reduced pH of 5.0. The HMUCNPs exhibited strong UCL intensity under 980 nm IR laser excitation. Furthermore, the intensity of green fluorescence was related to the loading content of DOX, which could be used to track and detect of drug release.Chapter 3:The monodisperse NaYF4:Yb,Er UCNPs with good uniformity were prepared by a facile hydrothermal route and modified by mesoporous silica (MSNs) and folic acid (FA). After modification, the UCL of the obtained UCNPs could be enhanced slightly due to the effective repair of surface defect. The EE(%) and DLC(%) of UCNPs@MSNs-FA to DOX was 37.3% and 11.2%, respectively, when pH was 7.4. The DOX release property exhibited strong pH-responsive, in which, the drug release could be greatly accelerated when pH was 5.0. The pH-responsive drug loading/releasing properties were greatly related to the electrostatic force and hydrophobic interaction force between DOX and UCNPs@MSNs-FA.Chapter 4:In this chapter, we developed a novel double-targeted drug delivery system (UCNPs-Fe3O4@MSNs-FA) based on optical-magnetic multifunctional composites. The good superparamagnetism allows it to carry out drugs to pathological site effectively to realize passive targeting. Meanwhile, FA was conjugated to the surface of UCNPs-Fe3O4@MSNs to realize active targeting via folate receptor (FR) mediating. The drug targeting efficiency is improved greatly due to the dual role of passive targeting and active targeting. In this section, we adopted a novel approach to compound UCNPs with superparamagnetic Fe3O4 NPs based on chapter 3. Unlike the traditional methods that use Fe3O4 NPs as core and design into core-shell structures, the reported method inlaid the Fe3O4 NPs into the the SiO2 coating layer with the advantage of convenient operations and mild reaction. The magnetic and UCL properties of UCNPs-Fe3O4@MSNs-FA were discussed in detail, and the drug storage/release properties were analyzed emphatically.Chapter 5:A novel optical-magnetic multifunctional nanorattle-type drug carrier (Fe3O4@SiO2@a-NaYF4:Yb,Er MUCNRs) was designed and fabricated through an ion-exchange process. The MUCNRs consist of rare-earth-doped a-NaYF4 shells, a SiO2-coated Fe3O4 inner particle and a hollow cavity between core and shells. Importantly, the hollow volume existed in the MUCNRs can accommodate a drug payload. The EE(%) and DLC(%) of Fe3O4@SiO2@a-NaYF4:Yb,Er MUCNRs to DOX were 60.7% and 18.2%, respectively, when pH was 7.4. However, the drug release might be greatly accelerated at the reduced pH of 5.0, which exhibited strong pH-responsive. This drug loading/releasing property will be of great importance in targeting therapy of cancer. Fluorescence spectra and magnetic test show that the obtained Fe3O4@SiO2@NaYF4:Yb,Er MUCNRs exhibited strong UCL property and good superparamagnetism, which can be used as a multifunctional drug delivery platform that integrate drug tracing with magnetic targeted drug delivery. Thus, the obtained MUCNRs have potentially broad application in the aspect of targeted therapy of cancer.