Multi-scale Materials And Devices And Their Applications In Tumor Diagnosis And Therapy

As a part of personalized medicine,the liquid biopsy needs only a few amount of sample from patients(e.g.blood,saliva,urine and so on)for disease detection and diagnosis.Currently,the research objects of liquid biopsy mainly include the circulating tumor cells(CTCs),the circulating tumor DNA(ctDNA)and the exosomes.Among them,CTCs could provide intact cellular information which has significant clinical applications in early diagnosis of cancer and prognosis in real time.However,the traditional biopsy needs the surgeon to obtain the lesion sample through cut,clamp or puncture,etc.which will increase the pain of the patients and could not monitor the condition of disease in real time.Increasingly,advances in medicine rely on understanding the multimolecular causes,effects and signatures of diseases.Personalized therapies targeted to highly specific disease sub-states now leverage insights into the molecular origins and signatures of these illnesses.Radiotherapy,chemotherapy and other traditional cancer treatment methods could kill part of the tumor tissue,but has a strong side effects on body’s normal tissues and cells.In order to overcome the deficiencies and problems of current methods for CTCs capture and release,molecule detection in live cells and cancer therapy,we used the microfluidic method and nanomaterial technology,and developed an electrochemical microchip to highly efficient capture and release CTCs,polydopamine(PDA)coated nanosensors for molecule detection,near infrared killing cancer cell and drug delivery.The key research findings as below:Firstly,we designed an electrochemical microchip for highly efficient CTCs capture,release and lyse.The mcirodevice consist of 25000 cactus-like micropillars.This micropillar array was fabricated from polydimethylsiloxane(PDMS)substrate by the conventional soft-lithography technology and then plated a gold layer by electroless plating method,results in the whole array electroconductive.The mcirodevice presented a capture efficiency of 85-100%for different cell lines in both buffer solution and whole blood.The isolated cells possessed a high viability and can be released intactly by electrochemical method with high efficiency for subsequent cell culture or gene mutation detection by sequencing.Furthermore,captured cells could be directly lysed via electrochemical method and the resulted solution can be used for detecting the mutant sites in gene by RT-PCR.Thus,the integrated multifunctional microdevice with promising applications in clinical diagnosis was well presented.Secondly,we designed a nanosensor,GNR@PDA,for long time microRNA imaging in live cells.The nanosensor consisted of gold nanorod core and PDA coating.The PDA coating layer could facial and direct immobilization of DNA strands via π-π interactions and hydrogen bonding.Fluorescent probe molecules(hpDNA)could be co-quenching by the GNR and PDA.The fluorescently labeled hairpin DNA strands(hpDNAs)that can recognize specific miRNA targets.In addition,the nanoprobes were very stable in cell culture medium and could detect miRNAs for several cellular generations.Our GNR@PDA probes show great promises in the disease diagnosis,long-term tracking cell differentiation and proliferation,isolation and identification of specific cell types,high-throughput drug screening and therapy.Thirdly,a bifunctional nanosensor,AgNTs/PDA,was introduced for molecule imaging in live cell and phototermal therapy.This nanosensor was consisted with triangular silver nanoprism core and PDA coating layer.The shape,Zeta potential and cytotoxicity,etc.of AgNTs/PDA were evaluated.And the nanosensor hold absorb in near infrared zone which could be used to kill cancer cells by phototermal effect.Fourthly,we introduced a multifunctional nanoparticle for molecule detection in live cells,PTT,drug delivery and MRI imaging.The PDA layer coating on the core-shell Fe3O4@PDA nanoparticle makes the nanosensor to use in molecule imaging and PTT.The mesopores were used to high dose drug loading and delivery and the inner Fe3O4 core could be applied to MRI imaging guided therapy.The Fe3O4@PDA nanoparticles showed significant promises in biomedicine,material separation and analysis,etc.In conclusion,we designed a novel electrochemical microchip for highly efficient CTCs capture,release and lyse in order to overcome the shortcomings of existing CTCs capture devices in the second chapter.In the next chapters,we synthesized a series of nanoprobes based PDA coating for molecules detection in live cells,drug delivery,PTT and MRI imaging.These nanoprobes have significant applications in tumor diagnosis and therapy.