Preparation Of LDH Multicomponent Drug Carrier And Its Cytotoxicity

Layered double hydroxides （LDHs for short） is becoming a new drug carrier with great application prospect due to its good biocompatibility, tunability of the layer spacing and a strong positive charge. Now, Study of LDHs as drug carrier has attracted researcher attention, but it has seldom been studied that LDHs combined with new types of nanoparticles in order to achieve better medicine effect. In this paper, we choose methotrexate （MTX） as the guest molecule and Mg/Al-LDHs as carrier to synthesize nanometer carrier compounds by combining Au and Fe₃O₄ nanoparticles. We explore the influence of the LDHs synthesis methods, structures and properties of nanometer compound inhibition for A549 lung cancer cells. The details are summarized as following:1. Methotrexatum intercalated layered double hydroxides （MTX/LDHs） nanocomposites were synthesized by four different routes, i.e., typical coprecipitation method, reverse-microemulsion approach, ion-exchange and mechanochemical-hydrothermal procedures. The different synthetic methods of MTX/LDHs nano composites were studied for influence of monodispersity and inhibition of cell toxicity. The results showed that monodispersity of MTX/LDHs synthesized by typical coprecipitation method and reverse-microemulsion approach was better. MTX/LDHs synthesized by coprecipitation method show most effective suppression effects. In addition, MTX/LDHs synthesized by coprecipitation method was specified as the studied model, and the phosphate belanced solution （PBS） with pH=7.4 was used to simulate the physiological environment of the human body. Researches show that the biodegradation process can be divided into three processes, i.e., the release of drug by ion-exchange, the subsequent destruction of LDHs structure and then the complete disintegration of LDHs. At last, LDHs pieces would be dissolved completely, forming Al（OH）3 and Mg2+.2. Au-cit and Au-MTX nanoparticles were synthesized by using seeds to grow. Au-cit and Au-MTX with different size were synthesized by regulating the concentration of golden seed and growth-promoting media. We explored the particle effect of size of gold nanoparticles on the cell toxicity. Layer-by-layer method was used in order to carry stronger negative charge for Au NPs. Then Au NPs was directly conjugated onto the surface of MTX/LDHs hybrid by electrostatic attraction to afford Au@PDDA-MTX/LDH NPs. Drug release studies and inhibition for lung cancer cells of Au@PDDA-MTX/LDH NPs were explored. The experiment results show that the Au@PDDA-MTX/LDH for synergistic hyperthermia ablation and chemotherapy was demonstrated to exhibit higher therapeutic efficacy than MTX/LDHs particles for cancer therapy.3. Fe₃O₄@MTX/LDH was synthesized by in-situ synthesis. Then Au NPs was directly conjugated onto the surface of MTX/LDHs hybrid by electrostatic attraction to afford Fe₃O₄@MTX/LDH-Au. The structures, properties and inhibition for lung cancer cells of Fe₃O₄@MTX/LDH-Au was explored.