Polymeric Nanotheranostic Agent For Multimodal Imagings Guided Multimodal Synergistic Therapy

Cancer has the characteristics of high incidence,high mortality rate,easy recurrence,easy metastasis,a serious threat to human health and life.As is known to all,chemotherapy is still the most widely used treatment method in clinical practice at present,and it is widely used in the treatment of various solid tumors,such as ovarian cancer,colorectal cancer,lung cancer and so on.However,chemotherapeutic drugs usually have problems such as poor water solubility,high toxic and side effects,and drug resistance acquired by cancer cells,which limits the efficacy of chemotherapeutic drugs.Photothermal therapy is a new means of tumor treatment.The basic principle is that the photothermal reagent radiates the tumor tissue after gathering at the tumor site.The photothermal reagent converts light energy into heat energy,thus producing local high fever and killing tumor cells.Early diagnosis of cancer also has crucial treatment,medical imaging technology has small damage to the human body,real-time imaging and long-term tracking,advantages,including magnetic resonance imaging,ultrasound imaging,CT imaging and optical imaging has been widely used in the diagnosis of tumor,but the inevitable need to use imaging reagents.The rapid development of modern nanotechnology provides a strong guarantee for the nano-co-delivery of chemotherapeutic drugs and imaging reagents.However,the integrated nano-co-delivery of chemotherapeutic drugs and imaging reagents often has some problems,such as small load of chemotherapeutic drugs/imaging reagents,uncontrollable drug proportion,and significant batch differences.Therefore,it is of great research significance and clinical application prospect to develop an integrated polymer nanodrug delivery system for diagnosis and treatment to realize the large and efficient delivery of chemotherapeutic drugs and imaging reagents.This thesis includes the following two parts:（1）A new nanodrug delivery system was designed and prepared PUCPt NPs.L-lysine diisocyanate（LDI）,Cis,cis,trans-[Pt（NH₃）₂Cl₂（OH）₂]（DHP）,cyanine dye HOCy OH synthesize hydrophobic polyurethane chain segments by addition polymerization reaction,and then synthesize the three-block polymer PUCPt with hydrophilic m PEG_5k-NCO.The PUCPt NPs were prepared by self-assembly.The results of dynamic light scattering（DLS）and transmission electron microscope（TEM）show that the mean particle size and PDI of PUCPt NPs are about 103 nm and 0.177,respectively,and the morphology is spherical.In vitro experiments investigated the stability of PUCPt NPs,drug release performance,and photothermal conversion performance in a simulated physiological environment,tumor acidic and reductive microenvironment,and 808 nm light conditions.Animal experiments investigated the near-infrared imaging performance,thermal imaging performance,photoacoustic imaging and CT imaging capabilities,and anti-tumor effects and toxic side effects of PUCPt NPs in H22 tumor-bearing mice.PUCPt NPs As an integrated nano-drug delivery system for diagnosis and treatment,it has certain application prospects in the anti-tumor chemotherapy-phototherapy combined therapy and imaging.（2）A PCP@DOX NPs system of chemotherapy-photothermal therapy was developed.The HOCy OH and cyclobutane tetradinanhydride（CBDA）were simply polymerized to obtain the hydrophobic polyester and the hydrophilic chain segment m PEG_5k-OH to obtain the amphiphilic polymer PCP.By co-assembly,the chemotherapeutic drug doxorubicin（DOX）was encapsulated into PCP NPs to obtain PCP@DOX NPs.The particle size,PDI,and morphology of PCP NPs and PCP@DOX NPs were investigated by DLS and TEM.The stability and responsiveness of PCP@DOX NPs were investigated by simulating the physiological environment and the tumor microenvironment.The photothermal conversion performance and thermal imaging capability of PCP@DOX NPs were investigated by in vitro photothermal experiments.We show the great potential of this multifunctional polymeric polymer nano-drug delivery system for multi-modal imaging.