Potent and Long-term Antibacterial Property and Synergy Mechanism of Layered Double Hydroxide-based Nano Composites

Author:Li Meng Xue

Supervisor:qian guang ren liu jian yong


Degree Year:2019





The abuse of organic antibiotics leads to the increasingly serious problem of drug-resistant bacteria.It is urgent to develop new antimicrobial agents.In order to avoid the emergence of drug-resistant bacteria caused by repeated addition of short-acting antimicrobial materials,the development of efficient and durable antimicrobial materials is extremely urgent.Organic antimicrobials are highly specific,but they decompose easily and may cause problems of drug-resistant bacteria.Inorganic antibacterial agents have the characteristics of safety,durability and broad antibacterial spectrum,but their pertinence is weak.Organic/inorganic nanocomposite antibacterial materials,which could make up the deficiency of single antibacterial agents,could take the advantages of each antibacterial agent and form complementary.According to the above idea,the layered double hydroxides(LDHs)with the regulation of cation ions on layers,anions in interlayers and oxidation of layers,were combined with the inorganic transition metals,organic antibiotics or inorganic metal oxides via a facile method in this paper.The phase structure and morphology were characterized by EA,XRD,FTIR and TEM/HRTEM.And the potent and long-term antibacterial performance against Staphylococcus aureus(S.aureus)and Escherichia coli(E.coli),biocompatibility and synergy antibacterial mechanism of LDH-based nanocomposites were explored.The main conclusions of this study are as follows:1.Mg on layers of MgAl-LDH was substituted with transition metal M(Zn、Cu、Mn、Ni、Co)with different metal molar ratios(M:Al=2:1 or 3:1)(M2Al and M3Al).The results showed that M2AI and M3Al had typical LDH structures.Particular morphology of Mn2Al/Mn3Al with ellipsoids,spherical and rod-like structures and Cu2Al/Cu3Al with rod-like shape existed.Cu2Al,Zn2Al,Ni2Al,Co2Al,Mn2Al and Mn3Al showed ≥50%antibacterial activity at~200-1500 μg/mL.LDHs containing Zn、Cu、Ni and Mn had ≥50%toxicity towards eukaryotic cells.2.A varied amount of an organic antibiotic Penicillin G(PG)was assembled with Zn2Al-LDH.PG was mostly adhered to the surface of Zn2Al-LDH,and a small amount of PG was randomly inserted between Zn2Al-LDH layers.The typical release profile of PG and 2n2+ from PG/LDH was a quick release,followed by a sustainable slow release.The antibacterial tests against E.coli demonstrated that PG/LDH with a suitable composition synergistically improved bacterial inhibition compared with free PG and pristine LDHs.PG/LDH showed a potent antimicrobial activity and maintained the activity for up to 10 days,significantly elongating the antibacterial effect compared with just 1 day for free PG in the same conditions.And PG/LDH contained antibacterial activity towards S.aureus.3.The LDHs nanocomposites containing single metal oxides(MO/LDHs)were obtained using layered double hydroxides as precursor via hydrothermal regulation of LDHs layers.ZnO/LDHs can be transformed from ZnAl-LDH to ZnO and ZnAl2O4 crystallites on Zn5(OH)8(NO3)2·2H2O layers at 200℃ for 2h to generate~30nm uniform ZnO nanoparticles(Zn3Al-200-2).Mn3Al-200-2 and Zn3Al-200-2 inhibited the growth of bacteria.Zn3Al-200-2 nanohybrids showed potent antibacterial activity at 100-300μg/mL for up to 4 days.4.The LDHs nanocomposites containing bimetal oxides(ZnxCu3-xO/LDH,x=0,1,2)were synthesized via hydrothermal regulation of LDHs layers and change of the molar ratio of Zn2+and Cu2+on the layers.Zn2CuO/LDH and ZnCu2O/LDH with Zn2+changed the rod structure of Cu3O/LDH and formed a flake structure.The comparison of antibacterial properties showed that~250 μg/mL Cu3Al-200-2 achieved>50%durable antibacterial property for 72h and ZnCu2Al-200-2 reached>50%antibacterial property at 175 μg/mL.5.The preparation method of LDH-based nano composites was facile and fast.Doping of metal oxides(MO/LDH and ZnxCu3-xO/LDH)was conducive to the expression of potent antibacterial performance,while doping of organic antibiotics(PG/LDH)was conducive to the expression of durable antibacterial performance.The efficient and durable antibacterial mechanism was mainly due to the synergistic effect of inorganic transition metal ions,organic antibiotics,ROS of inorganic metal oxide and adsorption of inorganic LDHs.With the increase of LDHs concentration,the adsorption effect of LDHs may be slightly stronger than that of metal ions,organic antibiotics and ROS.In this thesis,the research results revealed the potent and long-term antibacterial activity of LDH-based nano composites with facile preparation and regulation.In order to further study the work on avoiding drug-resistant bacteria in presence of economic LDH-based materials,this thesis laid a certain theoretical foundation and accumulated some experimental experience.