DNA-Templated Complex for Photothermal Imaging and Labeling of Cancer Cells

Author:Wang Gang Lin

Supervisor:ma zuo


Degree Year:2018





Nanomaterials have unique properties such as high specific surface area,high surface energy,and unique mechanical,thermal,electrical,magnetic,and optical properties.Therefore,in the past few decades,nanomaterials have been widely applied in many fields.Nanomedicine is one of the important fields of application.Phototheramal therapy(PTT)based on nanomaterials shows many advantages in the treatment of cancerous tumors,such as resistance to multiple tumors,adjustable absorption range of nanomaterials,integration of diagnosis and treatment,multi-functional synergistic treatment,and so on,which make themsubstantial promise forfuture clinical translation in cancer tumors.In this thesis,we reported a class of DNA-templated QDs-gold nanoparticle(GQC)for photothermal imaging and labeling of live cancer cells.In the first section,we prepared second generation(2G)DNA-QDs prepared via one step DNA-templated QDs synthesis,which is different from the first generation the first(1G)DNA-QDs prepared via conventional bioconjugation chemistry.2D DNA-QDs shows good photostablity and biocompatibility,which makes it good for biological imaging.In the second,we fabricated a class of DNA-templated gold nanoparticle(GNPs)-quantum dots(QDs)complex(GQC),which acts as a nonothermometer.Specifically,QDs photoluminescence(PL)could be activated at elevated temperature with a wide thermo-responsive range between 45 ?C and 70 ?C,which fits the temperature threshold for effective cancer cell ablation.Thirdly,three types of PT agents were synthesized and characterized.Next,we reported a class of DNAtemplated gold nanoparticle(GNPs)-quantum dots(QDs)complex(GQC)for PT sensing in vitro and in live cancer cells.The general applicability of GQC for intracellular PT sensing is revealed with three types of PT agents(gold nanorods,gold nanostar,prussian nanoparticle)with various PT perfommance.A gold correlation between mean PL of NIR-irradiated HeLa cells and surrouding termperature is obtained.In addtion,the QDs PL could be reserved posttreatment with the aid of capture DNA strands,which enables facile imaging and labeling of photothermally treated cells for long-term cell tracking.Lastly,we designed a novel platform based on PEI-FA and GQC and PEG-GNRsto abtain targered in situ monitoring of photothermal effect at cellular level.This way,photothermal therapy can be directed precisely on cancer cells without killing healthy cells in the vicinity.Long-term cell tracking and imaging-guided post-treatment therapy evaluation was achieved.In conclusion,we developed a novel type of photothermal sensor based on DNA-templated GNPs-QDs assembly for photothermal imaging and labelling of cancer cells.Specifically,this sensor is most responsive in ther range of 45 ?C~70 ?C,which corresponds to threshold temperature for efficient cancer cell ablation.Unlike conventional photothermal sensors,the GQC is used as an irreversible sensor in that the activated QDs PL is reserved post-treatment.This feature would allow not only measurement of locally administered PT dosage,but also facile identification and tracking of cancer cells post-treatment for therapy evaluation.It could be potentially applied to map and optimize depth-dependent PTT efficacy on a tumor model,or track the final destination of rare alive cells for tumor recurrence or metastasis.Also,it could be potentially used to monitor the PT damage to healty tissue for safety concerns.