The Applicaiton of Perylene Derivatives in Photodynamic Therapy,Antimicrobial and Biological Imaging

Author:Niu Niu

Supervisor:yu cong


Degree Year:2019





Perylene derivatives have been used in industrial dyes and coatings early in the discovery process due to their excellent optical,thermal,chemical stability,cheap availability and readily available properties.With the continuous development of science and technology and the continuous exploration of perylene,perylene derivatives have been found to have excellent photoconductivity,and are widely used in organic solar cells,semiconductor lasers and organic field effect transistors so on.With the advancement in the fields of biological sciences and biomedicine,the use of perylene derivatives in these fields has also evolved.For example,modified perylene derivatives have both photothermal therapy and photoacoustic imaging properties,and can be used as tumor therapeutic agents and optical imaging agents;some modified perylene derivatives have both photosensitivity properties,upon proper light irradiation,singlet oxygen can be effectively produced for photodynamic therapy;besides,based on the excellent fluorescence quantum yield of perylene,they can also be developed as a fluorescent imaging reagent for fluorescence imaging.Based on the photosensitive properties and fluorescent properties of perylene,we have developed a self-evaluation perylene-based photosensitizer for photodynamic therapy and photodynamic antimicrobial;a water-soluble benzoperylene derivative was synthesized.The cell membrane was imaged using its associate fluorescent signal.This paper mainly includes the following three parts:(1)Photodynamic therapy(PDT)is a promising noninvasive medical technique for tumor treatment.However,the efficacy of clinical PDT photosensitizer is often limited with weak chemical stability,low molar extinction coefficient,poor water solubility,high photobleaching rate,and lack of targeting capability.Thus,the search for ideal photosensitizer to overcome these limitations is essential.Herein,a highly water-soluble perylene probe PC4 is demonstrated as an efficient PDT photosensitizer.PC4 shows outstanding photo stability,very low dark toxicity,and can specifically target lysosome inside the cell.In addition,PC4 can enter and light up the dead cell nucleus during PDT treatment,thus offering a facile way to monitor the cell death process and evaluate the PDT effect.Finally,the excellent two-photon absorption property clearly suggests that PC4 is capable of two-photon deep tissue penetration and can be used for in vivo PDT and imaging.(2)Antimicrobial photodynamic therapy is a promising treatment of bacterial infection with the ability to kill both regular and multidrug-resistant bacteria.However,because most photosensitizers failed to effectively anchor or bind to bacteria membrane and the thick bacteria membrane provide the protection,this technique is hampered.Thus we utilized a perylene based probe PC4,has both appropriate topology to interact with lipid membrane as membrane-interact conjugated oligoelectrolyte(MICOE)and ability to generate singlet oxygen as an antimicrobial PDT agents.The PC4 showed a highly efficiency in antibacterial towards Gram-negative bacteria、Gram-negative bacteria and methicillin-resistant S.aureus bacteria.More interesting is,after killing the bacteria,PC4 could also enter into the interior of dead bacteria and light the cells with brighter green fluorescence.Thus it is easier and more convenient for us to evaluate treatment efficience after PDT.(3)Animal cells are surrounded and protected by complicated membrane structures,which make it vital for desirable dyes for cell membrane imaging.Herein,we designed and synthesized a sperime modified,water-soluble and positively charged benzoperylene probe(BP-3)for eximer-emissive,wash-free and turn-on cell membrane imaging.BP-3 possesses excellent chemical,thermal and photo stability.Furthermore,BP-3 can self-assembly in water with quenched emission,while self-assembly in organic solvents with bright exicmer emission.These types of aggregation can be reversible transited by simply change its solvent,accompanied with excimer emission ON/OFF change.Thus after being taking up into cells,the BP-3 can specifically light up the cell membrane due to the membrane hydrophobic environment.In addition,the ability of washing-free staining and fixed cells imaging of BP-3 was successfully demonstrated.The research provides a new type of membrane imaging agent and present a new application of benzoperylene based probes.