Preparation Of Layerded Double Hydroxides Nanocomposites Toward Cancer Phototherapy And Imaging

Layered double hydroxides (LDHs) are a typical class of layered materials with tunable cations in host layer and exchangeable interlayer anions, which have attracted considerable attention in the field of functional materials. Recently, LDHs based drug delivery system acts as a promising candidate for cancer therapy and diagnose, due to their satisfactory performance, facile preparation and good biocompatibility. In this study, the photothermal agent and photodynamic agent were introduced into the interlayer gallery of LDHs respectively via co-precipitation method. By adjusting the chemical composition of host layers and interlayer guests, the drug molecule state, arrangement and photofunctionality were studied. Furthermore, the application of composite materials for fluorescence imaging and cancer phototherapy was also investigated. The specific contents are shown as follows:1. A targeted photothermal agent (ICG-FA/LDH) was synthesized by co-intercalation of indocyanine green (ICG) and targeting folic acid (FA) into the LDH gallery, which showed an excellent near-infrared (NIR) imaging and superior photothermal therapy effect. XRD and FT-IR spectra confirm the co-existence of ICG and FA molecule in the interlayer region of LDH matrix; UV-vis-NIR spectroscopy proves the monomer state of ICG, which is a key factor for its photothermal conversion efficiency. Both a satisfactory NIR imaging and PTT effectiveness are demonstrated for the ICG-FA/LDH photothermal agent over in vitro tests performed with KB cells, with a cellular damage as high as 87.4%(ICG:8 ?g/mL; NIR irradiation energy:1.1 W/cm2, 12 min). The host-guest interaction inhibits the aggregation of ICG and enhances its photo-thermal transformation in the LDH gallery; the suitable particle size and biocompatibility of the ICG-FA/LDH composite facilitate the drug delivery, accounting for the excellent PTT performances. In addition, the photothermal agent ICG-FA/LDH displays good targeting capability and stability. It is expected that the unique ICG-FA/LDH with integrated fluorescence imaging and photothermal therapy can be potentially used in cell labeling and PTT area.2. We further fabricated a targeted photosensitizer ALA-FA-LDH through the coprecipitation-adsorption method. The composite material displays a regular platelet morphology and high drug loading. A series of characterization including FT-IR, UV-vis and zeta potential indicate that 5-ALA and FA are co-loaded on LDH laminate surface. In vitro tests performed with KB cells demonstrate a highly enhanced cellar uptake and excellent fluorescence imaging ability for ALA-FA/LDH. A satisfactory in vitro ALA-PDT effectiveness of the ALA-FA/LDH composite is obtained and it exhibits a cellular damage as high as 72.6% with an ultra-low dosage of 5-ALA (5 ?g/mL) and a weak irradiation at 635 nm (25 mw/cm2,20 min). The main reason for the excellent photosensitizer fluorescence imaging ability and ALA-PDT effectiveness can be ascribed to that the improved ALA uptake through clathrin-mediated endocytosis of LDH and targeted ability of FA.The LDHs based phototherapy agents explored in this work show prospective application in targeting drug delivery, fluorescence imaging and phototherapy.