Tumor Theranostics Based On Multi-wavelength Photoacoustic Effect

Tumors,especially malignant tumors,have become one of the major diseases endangering human health.At present,a large number of relevant clinical studies have been carried out on the diagnosis and treatment of tumor diseases,and got substantial progress and development.However,the occurrence and growth of tumor are a multi-factor and multi-step complexity process,which lead to the fact that most tumor diseases have entered an advanced stage when they are discovered and diagnosed.It will increase the difficulty of clinical intervention and lose the best time for treatment.Finally,it will bring serious physiological and psychological impacts to patients.Therefore,it is urgent to explore effective methods suitable for the early diagnosis and precise treatment of cancer,and completely overcome the worldwide problem of cancer.In clinical,doctors mainly applied mature medical imaging technologies and analyzed the pathological imaging results to diagnose the diseases.However,these imaging methods exist some limitations,and cannot give feedback timely in the early screening and clinical detection of tumor diseases.In terms of tumor treatment,the main strategies used in clinical practice are surgical resection,drug radiotherapy,and chemotherapy.However,these traditional treatment methods have the defects of large toxic side effects,low efficiency,and incomplete treatment for malignant tumor diseases.With the development of biotechnology,there are new tumor treatments with great clinical potential,such as photothermal therapy(PTT),photodynamic therapy(PDT),and immunotherapy,however,these methods also have some limitations with low drug delivery efficiency,poor timeliness,and complex treatment courses.In the past decade,the rapid development of photoacoustic imaging(PAI)has gradually attracted the attention of the biomedical field.PAI combines the characteristics of optical imaging and ultrasonic imaging,features with high image contrast and deep imaging depth.It can accurately reflect the optical absorptive information in the biological tissue and is extremely sensitive to blood absorption in tissues.Considering the physiological phenomenon during the early growth of tumors,the disease site will release a large number of angiogenic growth factors accompanied by abnormal angiogenesis,which is used to provide sufficient nutrients and energy for the tumor cells.Therefore,PAI has great advantages in the early diagnosis of tumor diseases with non-invasive,label-free,and wide range of use.Besides,for the precise treatment of tumors,we use a photoacoustic effect-based precise drug delivery method,which was discovered by our laboratory,realizing efficient nanoparticles delivery to the tumor disease site with micron-level accuracy.Combined with the excellent optical properties of nanoparticles,we achieved effective treatment for tumor diseases.Specifically,the main research contents of this dissertation include:1.We build a special PAI system to analyze the unique photoacoustic spectral characteristics of various organs at the same imaging depth in the range from visible light to near-infrared on the macro level.In addition,we explore the photoacoustic spectral characteristics of organs at different imaging depths according to the actual application requirements.The results provide a reference of the excitation laser wavelength that can achieve the best imaging effect for specific PAI requirements.It sets a foundation for the subsequent photoacoustic tumor imaging research and the design of nanoparticles with excellent optical properties.2.Based on the photoacoustic molecular imaging technology,we develop a multi-wavelength acoustic resolution photoacoustic microscopy(AR-PAM)system and designed different kinds of biomolecular probes with partners to carry out the research of inflammation and tumor diseases in animals.By observing the internal structure of the tumor and monitoring the aggregation and distribution of molecular probes at the disease site,we guide the external intervention and treatment methods to achieve a better therapeutic effect.3.We built a desktop multi-wavelength optical resolution photoacoustic microscopy(OR-PAM)system to observe the vascular network changes in tumor early growth.Based on the precise drug delivery system,we designed an integrated tumor platform with early diagnosis,precision treatment,and prognostic monitoring.4.We design a miniaturized PAI system and assemble a handheld single-wavelength optical resolution photoacoustic microscope.Through the basic phantom and in vivo animal brain imaging experiments,we test and evaluate the performance of the system.Besides,we establish the ischemic stroke and hemorrhagic shock models to observe and analyze the hemodynamic changes of the animal.All the results lay a solid foundation and accumulate rich experience for the subsequent construction of a handheld multi-wavelength photoacoustic laparoscope.5.We develop a multi-wavelength optical resolution photoacoustic laparoscope.Combined with the precise drug delivery system,we perform some relevant experiments on different kinds of tumor models and multiple abdominal organs.The experiments demonstrate the capability of the laparoscope in actual drug delivery,and it also provides a potential tool for future clinical research on deep organ diseases.Summarized,this dissertation develops different kinds of PAI systems and conducts a series of studies on early diagnosis and treatment for tumors.It demonstrates the feasibility of PAI technology in the diagnosis and treatment of tumor diseases,and provides a solid foundation for its extensive and mature application in future clinical research.