Nano-assembly Of Organic Conjugated Polymers For Antibacterial And Antitumor Therapy

Conjugated polymers are a kind of organic functional material with large ? conjugated structure.They not only have good optical properties,such as strong light capture ability,high quantum yield,good optical stability,but also possess the advantages of adjustable energy band and good biocompatibility.In addition to the advantages mentioned above,conjugated polymer nanoparticles also own the space advantages and facile modification of nanoparticles.Therefore,conjugated polymers and their nanoparticles have been widely studied in biosensing,imaging,the diagnosis and treatment of diseases.Diseases caused by bacterial infections have always threatened human health,and the emergence of drug-resistant strains has made the problem even worse.How to effectively treat bacterial infection related diseases,there are still many problems.For example,Gram-negative bacteria are difficult to kill compared with Gram-positive bacteria due to the protective outer membrane structure.Residual active antibiotic after treatment makes bacteria antibiotic,antibacterial treatment brings the damages to normal cells,and so on.Besides,bacteria are considered to trigger the formation of tumors.Since chemotherapy has serious side effects,it is urgent to develop more effective treatment.Therefore,innovative strategies and the development of effective antibacterial and anti-tumor materials are the key points to solve the current threat to human public health.It is crucial to reduce social and economic costs and improve people's quality of life.In view of the current dilemma,in this thesis,we takes advantage of the properties of conjugated polymer nanoparticles and the specificity of biomolecules to design and construct a series of nanometer self-assembly systems based on conjugated polymer.The applications of these assemblies in antibacterial and anti-tumor therapy are systematically investigated.Corresponding materials with low toxicity and high efficiency to kill bacteria and tumor cells are obtained.The main research contents and experimental results are as follows:1.In order to obtain effective antibacterial materials,conjugated polymers with hydrophobic backbones and hydrophilic side chains of protonated primary amine salts are innovatively designed.The novel antibacterial conjugated polymer nanoparticles(PDCP-NPs)formed by self-assembly have high positive charge density and multiple membrane binding sites.The morphology of the nanoparticles is spherical with uniform size,and the size is about 180 nm.By effectively binding and destroying bacterial cell membranes,the nanomaterials can kill bacteria with no obvious cytotoxicity,especially for Gram-negative bacteria.In addition,PDCP-NPs can image bacteria and treat the bacteria infected wounds of mice.The antibacterial effect of PDCP-NPs is better than the commonly used antibiotics,and there is no obvious damage to the main organs and tissues of mice.This study provides a compatible antibacterial material with high antibacterial activity and low cytotoxicity,and proposes a new strategy for the development of high-efficiency antibacterial material with good biological safety.2.Based on the control strategy,the nano-assembly with controlled bactericidal activity mediated by biomolecules is developed and applied to the treatment of infected wounds in mice.By using calf thymus DNA and DNase I enzyme to regulate the interaction between CPNs-H and bacteria,the antibacterial activity of the assembly displays the reversible states of "closed" and "opened".The CPNs composed of fluorene and dithiophenyl benzothiadiazole unit can emit red light.The surface of CPNs is covalently modified with H33258 dye which has antibacterial activity and a blue fluorescence.The obtained composite antibacterial material has double-channel imaging capability for bacteria,which can provide a basis for the amount and frequency of medication.Through the self-assembly between antibacterial nanoparticles and DNA,and the disassembly process mediated by DNase I enzyme,the assembly shows controlled antibacterial activity and can treat infected wounds of mice in a controlled way.In this work,we propose a new strategy against drug-resistant bacteria and develop a kind of antibacterial self-assembly based on biomolecular regulation.These results also provides a simple and friendly way to solve the dilemma of drug resistance and theoretical guidance on designing in situ controlled bactericidal system for treatment of bacterial infection-related diseases.3.Based on the nano self-assembly mode,a good idea of using the anti-tumor properties of conjugated polymer,biological molecules and light to regulate the killing of tumor is proposed.Conjugated polymer PFFBT with positive charges can assembles with human serum albumin(HSA)with negative charges to form biocompatible self-assembly PFFBT@HSA by hydrophobic and electrostatic interactions.The morphology and properties of the self-assembly are studied by using related characterization and analysis methods.By introducing HSA,PFFBT@HSA has longer phosphorescence life than PFFBT,and produces more reactive oxygen species by sensitizing oxygen efficiently under light.The assembly makes full use of the advantages of biomolecules,which can reduce the biotoxicity and make the dark toxicity in the “off” state.After irradiation,PFFBT@HSA can generate more reactive oxygen species than PFFBT,which enhances the anti-tumor ability of assembly and achieves the anti-tumor of "0+1>1" amplification effect.Therefore,relevant experiments are carried out to inhibit and kill tumor cells in vitro and in vivo.The results show that PFFBT@HSA can effectively inhibit and kill tumors in mice without causing obvious damage to other organs and tissues.In this work,biological molecules and physical technique(light)are used to regulate the anti-tumor process of conjugated polymers,the results provide a new approach and experimental reference for the design of controllable drug activity by using endogenous molecules and simple physical techniques.