¹⁹F-Magnetic Resonance/Fluorescence/Photoacoustic Multimodal Imaging Of Lung Cancer

Lung cancer is one of the malignant tumor with the fastest increase in morbidity and mortality and the greatest threat to people's health and life.Early accurate diagnosis is crucial to improve its cure rate.Therefore,the development of accurate and effective diagnostic methods has attracted widespread attention.Magnetic resonance imaging(MRI),as a non-invasive molecular imaging method,has no ionizing radiation,is suitable for soft tissues imaging and has no penetration depth limitation.19F-MRI has also gained more and more attention in biological imaging and disease diagnosis due to it's lack of endogenous background interference,but it still has the disadvantage of low sensitivity.While fluorescence imaging(FLI)has very high sensitivity but limited by low penetration.In addition,photoacoustic imaging(PAI)combines the high sensitivity of optical imaging and the good penetration depth of acoustic imaging,it can obtain high-resolution images of tumor microvascular structures.Thus,combining 19F-MRI with FLI and PAI can fuse anatomical information with better spatial resolution and biological information at the molecular level with high sensitivity.Based on the advantages and disadvantages of 19F-MRI,fluorescence imaging and photoacoustic imaging technologies for the specific detection of lung adenocarcinoma cells and tumors,the main contents of this dissertation are shown as follows:In chapter two,a one-pot microwave synthesis to fabricate fluorinated silicon nanoparticles(19FSiNPs)was presented.The modified microwave assisted synthetic strategy avoids tedious and complicated manipulation required for the synthesis and modification of SiNPs.The resulted 19FSiNPs exhibit strong fluorescence,high 19F-MRI sensitivity,favorable biocompatibility and excellent aqueous solubility.The targeted dual 19F-MR/fluorescence imaging study of A549 cells are achieved by grafting specific RGD peptides onto these nanoparticles.In vivo tests show that 19FSiNPs are suitable for 19F-MRI and fluorescence imaging of the tumor.In chapter three,lung cancer A549 cell membrane was extracted and coated on theranostic nanoagents where perfluoro-15-crown-5-ether(PFCE)was encapsulated by poly(D,L-lactide-co-glycolide)(PLGA)as a core,with indocyanine green(ICG)loaded inside,denoted as AM-PP@ICGNPs.A series of in vitro experiments prove that AM-PP@ICGNPs have good stability,biocompatibility and high photothermal efficacy.AM-PP@ICGNPs can specifically target and recognize homologous A549 cells and produce photothermal toxicity to cells under near infrared laser irradiation.The study in chapter four is based on the research work in chapter three,the in vivo tumor targeting effects,multimodal imaging capabilities and antitumor phtotothermal effects of AM-PP@ICGNPs were further evaluated in A549 tumor bearing nude mice.Upon homologous targeting to A549 tumor after intravenous injection of AM-PP@ICGNPs,FLI reveals time-dependent tumor homing of NPs with high sensitivity,19F-MRI provides tumor localization of NPs with high spatial resolution and PAI can illustrate the heterogeneous distribution of NPs inside the tumor.What's more,AM-PP@ICGNPs accumulated in tumor area exhibit prominent photothermal effect under near infrared laser irradiation and realize enhanced antitumor response in vivo.These benefits,in combination with it's excellent biocompatibility and little systemic toxicity,make AM-PP@ICGNPs a promising multifunctional agent for effective tumor imaging and ultimately achieve highly efficient photothermal therapy.In summary,we have designed and constructed multifunctional probes with SiNPs and PLGA as carriers for specific recognition of lung cancer cells.The constructed probes can also selectively target lung tumors to achieve simultaneous diagnosis and treatment applications.