Preparation And Properties Of Phenylboroni Acid Functionalized Multiple Responsive Nanometer Therapeutic Agents

Nano drug carrier material with tumor microenvironment stimulus responsive,for its good biocompatibility and easy functionalized modifications,has a good application prospect in large area of development and plays an important role especially a variety of treatment methods in tumor treatment combined with the combination therapy within the tumor response of nano drug delivery system.In this paper,multiple stimulus-responsive drug carriers targeting sialic acid?SA?receptors were constructed through the structure of benzene boric acid and boric ester,and the nano-delivery system integrating diagnosis,chemotherapy and PDT was constructed by using modifiable groups on the surface of polymer nano-drug carriers,so as to effectively diagnose and prevent metastasis in the early stage of tumors.The main research contents of this paper are as follows:1.A pH-sensitive amphiphilic polymer Poly?ethylene glycol?-phenylborate-poly?caprolactone??mPEG-PBE-PCL?linked by a borate structure was prepared by ring-opening polymerization of?-caprolactone??-CL?which was initiated by a benzene-borate-containing polyethylene glycol macromolecule?mPEG-PBE-OH?.The polymer was self-assembled and formed a"core-shell"nanomicelles structure in aqueous environment and loaded doxorubicin?DOX?in the micellar core.The morphology and particle size of the prepared micelles were observed by transmission electron microscopy?TEM?and dynamic light scattering?DLS?,and the micelle drug loading and drug loading efficiency were analyzed by ultraviolet absorption detection.The pH-sensitive release properties of micelles and in vitro cytotoxicity were verified.The results showed that the polymer micelles had a low critical micelle concentration,self-assembly forms spherical micelles of about 127 nm,and a high loading capacity for DOX,the polymer had good pH response and biocompatibility.The loaded DOX was released in weak acidic environment of tumor cells and was delivered effectively to nucleus.DOX@mPEG-PBE-PCL had a similar antitumor activity against murine melanoma B16F10 cells to free DOX·HCl.2.A novel amphiphilic polymer with pH/ROS dual response PBA targeting,poly?Phenylboronic acid?-poly?Lipoic acid amide?-polyethylene glycol-poly?Phenyl boronate??PBA-TOA-PEG-PBE?,was synthesized.DOX was embedded in its"core"through self-assembly,and CdHgTe was coated in the formed nano-micelle through coordination with polythioctamide.The morphology and particle size of the composite micelle were characterized by TEM and DLS.The drug-and pharmacokinetic properties as well as the optical properties of quantum dots were characterized by UV/Vis and fluorescence detection.The photo-induced production of reactive oxygen species?ROS?by CdHgTe was studied.Under the hypoxic environment of tumor cells,CdHgTe QDs can generate ROS by laser irradiation,which has the feasibility of applying to tumor PDT.The polymer carrier has good biocompatibility,and the composite nano-micelle significantly inhibits the proliferation of B16F10 melanoma cells,which has a good synergistic therapeutic effect.3.A predrug DTPA-PVI-PEG-P?PB-DOX?with dual pH/ROS response was formed in weakly alkaline solution by a block polymer DTPA-PVI-PEG-PBA and DOX.CdHgTe@DTPA-PVI-PEG-P?PB-DOX?composite nano-micelle was formed by functional imidazole block and CdHgTe.The morphology and particle size of the composite micelle were characterized by TEM and DLS.The pH/H₂O₂ sensitive release properties of the prodrug micelles in vitro were tested by UV/Vis and fluorescence detection.The cytotoxicity of the compound nano-drug was verified by in vitro cell test.The results showed that photoinduced CdHgTe generated ROS in B16F10 cells,promoted the release of drugs,and could be used for the photodynamic therapy of hypoxic cells.Compound micellar CdHgTe@DTPA-PVI-PEG-P?PB-DOX?effectively plays the role of combined therapy,and significantly inhibits the proliferation of B16F10 cells compared with DOX.In vivo B16F10 tumor SPECT imaging and biological distribution of ^99mTc-DTPA-PVI-PEG-P?PB-DOX?@CdHgTe,which was chelated with ^99mTc via DTPA,indicated that the composite nano-micellar was effectively enriched at the tumor site.