Multifunctional Nanoparticles Responsive To Tumor Microenvironment For Cancer Diagnosis And Treatment

At present,tumor is still an urgent public health problem in the world,which not only affects people’s physical and mental health,but also has a great impact on the harmony of family and society.In recent years,nanotechnology has become one of the research hotspots in the treatment of cancer through the interdisciplinary research of materials science,biomedicine and pharmacy.The multidisciplinary design and preparation of multifunctional nanoparticles can effectively realize cancer diagnosis,treatment and real-time monitoring of drug delivery.Poly（amino acid）is a kind of biodegradable and biocompatible polymer materials.Due to its special physical and chemical properties,it has been widely used in biomedical fields such as drug carrier and tissue engineering.Therefore,it is urgent to develop and design intelligent responsive poly（amino acid）materials for anti-tumor research.As an inorganic semiconductor material with excellent optical properties（such as excellent optical stability,high photoluminescence quantum yield,narrow emission spectrum and extended service life）,quantum dots have been widely used in the field of diagnosis and treatment of diseases.Combining the excellent performance of the two will be helpful to the development and application of multifunctional nanocarriers.Therefore,in this paper,a novel tumor microenvironment-responsive nanocarrier was designed and prepared for in vivo protein drug delivery and real-time monitoring imaging.In this paper,Cd Se@Zn S/Zn S quantum dots with thick shell and low toxicity with green fluorescence and high luminescence were prepared by high temperature organic phase method.Then,the platform ligand PEG-b-PBLG was synthesized by ring-opening polymerization using PEG-NH₂ as macromolecular initiator,and the intermediate poly（amino acid）ligand PEG-b-P（ED）LG was synthesized by ammonification reaction.On this basis,by grafting lipoic acid on some side chains as anchors,PEG-P（ED-LA）LG polymer ligands with"anchoring"groups were prepared,which were used to replace the original ligands of quantum dots.To obtain the final polymer ligand,the remaining free amino group on the side chain of the intermediate ligand reacts with 2,3-dimethylmaleic anhydride to convert the amino part of the side chain to the carboxyl group.Then,through the surface ligand exchange strategy,the pH-sensitive PEG-P（ED-DLA-DMA）LG ligands were used to replace the hydrophobic ligands on the surface of quantum dots,and the QD-PEG-P（ED-DLA-DMA）LG nano-carriers with green luminescence,water solubility and compact accumulation were prepared;the multifunctional nanocarrier surface and cytochrome C were used to realize the payload of protein drugs through the charge interaction and hydrophobic interaction between them.The experimental results showed that this drug-loaded nanocarrier could not only improve the blood circulation time and biocompatibility,but also effectively load cytochrome CC to significantly inhibit the growth of tumors.In addition,the pH-responsive ability to trigger charge conversion enables the QD-PEG-P（ED-DLA-DMA）LG-CC nanocarrier to kill cancer cells more effectively than the conventional comparison group,namely QD-PEG-P（ED-DLA-SA）LG-CC.Therefore,the multifunctional nanocarrier constructed in this paper is helpful to realize the goal of targeting malignant cancer with integrated visual therapy.