In Situ Polymerization In Tumor Of Water-soluble Aniline Derivative And Its Application In Phototheranostics

The tumor lesion area has a unique microenvironment that is different from healthy tissues,such as mild acidity,overexpressed hydrogen peroxide(H₂O₂),high levels of GSH,low catalase activity and hypoxia,etc.These specific microenvironmental characteristics not only provide a suitable environment and nutrition for tumor occurrence,proliferation and metastasis,etc.,it also provides favorable conditions for realizing the controllable construction of cancer diagnostic and therapeutic agents in the tumor with nanomaterials,so the utilization of tumor microenvironment(TME)has attracted the attention of many researchers.In recent years,in situ biosynthesis is an emerging strategy for synthesizing tumor-specific diagnostic and therapeutic agents,it mainly uses the characteristics of TME to make nanomaterials or responsive molecules change at the tumor site,such as near-infrared absorption,consumption of GSH to enhance chemokinetic therapy,and precise release of chemotherapeutic drugs in response to slightly acidic conditions have achieved more effective tumor treatment.This strategy can not only improve the spatial selectivity of materials,but also minimize the non-specific damage of materials to normal tissues.At present,the nanotherapy platform designed based on the microenvironment of tumor overexpression H₂O₂ mainly focuses on using the peroxidase activity of nanomaterials to catalyze the production of H₂O₂ to generate·OH to achieve Chemokinetic Therapy(CDT).In addition,the design of small organic molecules or nanomaterials with high specificity and sensitivity can perform accurate in vivo imaging and specific treatment after overexpression of H₂O₂ in response to the tumor microenvironment,achieving selective enhanced cancer diagnosis and treatment,so it has also aroused great interest among scientific researchers.In situ tumor polymerization triggered by overexpression of H₂O₂ provides a new way for tumor specific diagnosis and treatment.but in-situ polymerization must be compatible with the complex tumor microenvironment,because this environment contains numerous molecules and functional groups that can potentially prevent or quench the polymerization reaction.Therefore,it is still a huge challenge to use the tumor H₂O₂ overexpression microenvironment to manipulate the biosynthesis of polymer monomers to obtain functional polymer materials to achieve enhanced tumor-specific diagnosis and treatment.Based on this,this thesis designed and prepared a sulfonic acid-modified water-soluble aniline-derived monomer,and carried out the study of tumor in-situ polymerization and phototheranostic related applications of this monomer.The main contents are as follows:Chapter 1:The current research status of photothermal therapy,photothermal reagents,synthesis and biological application of polyaniline and its derivatives,biological in-situ polymerization,photoacoustic imaging and integration of diagnosis and treatment are briefly introduced.Based on this,the topic selection ideas and research significance of this article are put forward.Chapter 2:The aniline-derived monomer(PSA)with good water solubility was prepared by a one-step method,use LC-MS,FT-IR and other characterization to determine the successful preparation of PSA monomer.Then,through a series of characterization,the physical and chemical properties of the polymer PPSA obtained by the oxidative polymerization of the PSA monomer under the action of the·OH generated by the decomposition of hydrogen peroxide catalyzed by the HRP enzyme are carried out in detail.In-depth study of the photothermal conversion performance,photothermal stability and the photoacoustic imaging performance of the polymer PPSA in the NIR-I and NIR-II,and study of the response performance of the PSA monomer to the concentration of hydrogen peroxide,the experimental results show that PSA monomer is a water-soluble aniline-derived monomer that responds well to hydrogen peroxide and can quickly oxidize and polymerize to obtain polymers,the obtained polymer has good application potential in photoacoustic imaging and photothermal therapy in the near-infrared region.Chapter 3:Based on the research on the performance of PSA monomer and polymer PPSA in the previous chapter,the tumor in situ polymerization of PSA monomer and its application in NIR-I photoacoustic imaging and photothermal therapy have been systematically studied.The results show that:PSA monomer has the potential to achieve efficient and rapid in-situ polymerization in tumor cells or tumor sites.The self-doping effect of the sulfonic acid group makes the polymer PPSA obtained by in-situ polymerization exhibit excellent photoacoustic imaging performance and photothermal effect.In vitro cell and animal experiments have proved that PSA monomer can be successfully converted into polymer PPSA by oxidative polymerization in tumor cells or tumor sites,so as to achieve excellent photoacoustic imaging to guide tumor photothermal treatment.Therefore,this work provides a new way for polymer monomers to use the characteristics of tumor microenvironment to synthesize functional polymers in situ and apply them to the multifunctional diagnosis and treatment of tumors.Chapter 4:Compared with the NIR-I,the laser in the NIR-II has inherent advantages,such as deeper tissue penetration and higher maximum allowable exposure(MPE)of external light sources.On the basis of the study of photoacoustic imaging and photothermal therapy in the NIR-I in the previous chapter,we further explored the in-situ polymerization of PSA monomer and its photoacoustic imaging and photothermal therapy in the NIR-II.In vitro cell and animal experiments have proved that PSA monomer can be successfully converted into polymer PPSA by oxidative polymerization in tumor cells or tumor sites.Due to the self-doping effect of sulfonic acid groups,PPSA has strong absorption in the NIR-II,it can be used as an ideal photoacoustic imaging contrast agent and photothermal reagent in the NIR-II for photothermal therapy guided by photoacoustic imaging visualization.Therefore,this work provides a new idea for using the characteristics of the tumor microenvironment to manipulate the in-situ polymerization of aniline-derived monomers and achieve enhanced NIR-II tumor-specific light diagnosis and treatment.