Layered Double Hydroxides Based Materials Toward Bioimaging And Cancer Therapy

Layered double hydroxide is one kind of typical two-dimension material with versatile chemical composition and morphology. The tunable metal elements in host layers and the exchangeable property of interlayer anions have drawn tremendous attention, which have been widely studied as carriers in the molecule storage and gene/drug delivery.In this dissertation, several drugs, imaging agent and targeting agent were co-intercalated into the LDHs gallery, so as to obtain novel biomedicine materials. The structure and host-guest interactions of these composite materials were investigated based on an experiment-calculation combination study, and their bioimaging and therapy toward cancer cells were thoroughly explored.The specific contents are shown as follows:1. A supermolecular nanovehicle based on the intercalation of FA and DOX into the LDHs gallery was successfully prepared. The XRD result confirms that DOX and FA are intercalated into LDH successfully. The DOX-FA/LDHs material shows a uniform morphology with particle size of-171 nm. In vitro experiments demonstrate that the DOX-FA/LDHs exhibits good imaging property and apparently increased targeting cell uptake. Furthermore, the DOX-FA/LDHs nanovehicle can produce a strong suppression on the proliferation of HepG2 cells but a low toxicity to the normal L02 cells, owing to the over-expression of FA toward HepG2 cells. The enhanced biocompatibility would guarantee its application in cancer imaging and therapy.2. A novel supermolecular nanovehicle was fabricated by the co-intercalation of FA and DOX into Gd3+ doped LDH, followed by the chemical adsorption of FITC. The resulting FITC/FA-DOX/Gd-LDHs presents uniform morphology with particle size of ～178 nm and superior stability. Furthermore, the layered material demonstrates dual-modal imaging based on fluorescence signal from FITC and MRI from Gd3+ in LDHs host layers. In vitro experiments show that the FITC/FA-DOX/Gd-LDHs exhibits an obviously enhanced targeting uptake and anticancer activity toward KB cells. The superior dual-modal imaging properties would guarantee its application in cancer imaging and therapy.3. The dual-modal imaging and synergistic PDT/PTT treatment were performed by the co-intercalation of ZnPc, ICG, FA into the gallery of Gd3+doped LDHs. The as-obtained ZnPc-ICG-FA/Gd-LDHs displays a uniform morphology and enhanced stability. Moreover, this layered material presents dual-modal imaging with excellent fluorescence and MRI signal. Upon the 808 nm irradiation, ICG can be triggered to produce sufficient hyperthermia which induces the cell apoptosis (PTT treatment). Simultaneously, ZnPc is activated by the transferred energy from ICG to generate 1O2 which results in the apoptosis (PDT treatment). The co-intercalated FA significantly enhances the uptake by HepG2 cells. Therefore, this work demonstrates a successful paradigm for the design and fabrication of layered materials by the incorporation of imaging agent, therapeutic drug and LDHs, which can serve as a promising candidate in dual-modal imaging and targeted synergistic therapy.