Synthesis Of PH-responsive Degradation Nanoprobe And Its Application In Tumor Imaging And Therapy

Imaging-guided photodynamic therapy（PDT）can simultaneously achieve molecular imaging and photo-triggered therapy,and has received more and more attention from biomedical researchers in recent years.Although organic fluorophores can be designed as nanomaterials that are less toxic and more suitable for imaging an d treatment in biomedical applications,many nanoparticles synthesized based on organic fluorophores exhibit Aggregation-Caused Quenching（ACQ）when concentrated solutions or aggregates quenching phenomenon,which leads to a decline in imaging quality and treatment effectiveness.Fortunately,Tang and colleagues discovered the phenomenon of Aggregation-Induced Emission（AIE）in 2001,which is exactly the opposite of the ACQ phenomenon,which caused a wave of research on the latest cancer treatments.Among m any established AIE systems,push-pull electronic structure systems based on Tetraphenyl Ethylene（TPE）often have excellent photosensitivity,and their AIE characteristics have been widely used in PDT.Therefore,combined with previous research,we ration ally modify the two TPE-type photosensitizer molecules to improve their hydrophilicity and biocompatibility.Among them,the change of pH value is used as a switch to respond to TPE-type photosensitizer molecules.Specific research has been carried out in the following two aspects:1.A pH-responsive biomineralized nanoparticle for tumor aggregation-induced emission detection and photodynamic therapyA novel calcium carbonate-modified photosensitive molecule for tumor acid response and photodynamic therapy is reported here.CaCO₃ nanocarrier was prepared by using bovine serum protein as the skeleton for the first time and loaded with a new type of aggregation induced luminescence photosensitive molecule（TPE-Br）.The TPE-loaded NPs have small sizes（100±10 nm）with good water dispersion and stability.With the increase of acidity（pH=7.4～5.0）,internal TPE-Br molecules are released gradually.The released molecules accumulate through hydrophobic interaction,fluorescing and generating photodynamic therapy u nder an external light source.The nanocarrier has good biocompatibility and biodegradability,and the internal TPE-Br molecule has good fluorescence imaging performance and photodynamic therapy performance.Cell experiments have confirmed the great potential of nanoparticles in tumor imaging and treatment,providing further guidance for diagnosis and treatment in mice2.A pH-responsive biodegradable nanoparticle for tumor imaging detection and simultaneous photodynamic therapy and chemodynamic therapyIn pathophysiology,most human diseases are related to abnormal physiological environment,and they are considered as clinical signs of some diseases.Compared with normal tissue cells,tumor tissue cells generally have a relatively low pH value.Using this feature,a pH-responsive biodegradable nanoparticle was designed:using Ca CO₃ nanoparticles as carriers,tannic acid（TA）and Ca CO₃ nanoparticles are deposited on Ca CO₃ nanoparticles by simple mechanical stirring,TPE-I molecules with aggregation-induced luminescence and photodynamic therapeutic effect are coupled to Ca CO₃-TA nanoparticles throughπ-πstacking and electrostatic interaction;In order to improve the therap eutic effect,Mn²⁺with Fenton-like therapeutic effect in the presence of physiological buffers HCO₃^-/CO₂ and H₂O₂ also binds to the particles throughπ-πstacking and electrostatic action to form the final target nano-final particles.The prepared nanoparticles have good hydrophilicity and biocompatibility under normal physiological conditions,and their fluorescence intensity is relatively low,but once the pH of the solution drops,the released TPE-I molecules aggregate with each other through hydrophobic interaction to induce luminescence and under the action of external light source for photodynamic therapy.In addition,the released Mn²⁺produces a large amount of·OH in the presence of HCO ₃^-/CO₂ and H₂O₂,which is used for chemodynamic therapy.The sp eed of fluorescence recovery of nanoparticles in solution under different pH conditions and the changes of ABDA and methylene blue absorption values are used to verify the potential application of nanoparticles in aggregation-induced luminescence detection and treatment,and provide further imaging and treatment in tumors theoretical basis.