Construction Of Near-infrared Quantum Dots And Upconversion Nanoparticles-based Nanoplatforms For Tumor Theranostics

With the fast development of nano-biotechnology,near-infrared?NIR?I-III-VI CuInS quantum dots?QDs?and NaYF₄ upconventional nanoparticles?UCNs?have attracted considerable attention in the field of tumor diagnosis and therapy.However,most of high-performance CuInS QDs and NaYF₄UCNs are normally hydrophobic and could not be directly used for biomedical applications.Therefore,we herein aim at developing a serious of QDs and UCNs-based fluorescence nanoplatforms for tumor diagnosis and therapy via multifunctional assembly technique.Firstly,inspired by the specificity of acid tumor microenvironment,a smart tumor extracellular pH-responsive CuInS QDs nanoprobe is developed by encapsulating CuInS QDs into the assembly of lauric acid and 2,3-dimethylmaleic anhydride modified ?-polylysine??-PL-g-LA/DMA?for tumor cell-specific imaging.The results show that the nanoprobe possesses a uniform size of 40 nm,good chemical stability,low cytotoxicity and negative charge at pH 7.4.Once exposed to pH of 6.8,it swiftly reverses its surface charge to positive in 20 minutes.Moreover,the sensitive QDs nanoprobe displays significantly enhanced cell uptake into He La cells at pH 6.8 than non-sensitive ones.Secondly,a highly photostable hyperbranched polyglycerol?h PG?-based QDs nanoplatform is developed by incorporating CuInS/Zn S QDs into the assembly of our tailored h PG derivatives,amphiphilic h PG-alkyl chain?h PG-C12?and h PG-triphenylphosphonium?h PG-TPP?for mitochondria-specific tumor cell imaging.The results show that the QDs@h PG-C12/TPP nanoprobe possesses low cytotoxicity,low specific adsorption and mitochondria-targeted imaging ability.Compared with commercial mitochondria dyes,this QDs nanoprobe displays superior photostability under continuous laser irradiation.Moreover,drug-loaded QDs@h PG-C12/TPP displays an enhanced tumor cell killing efficacy than non-targeted ones.Thirdly,we herein develop a multifunctional upconversion nanoparticle system for image-guided photodynamic therapy?PDT?and chemotherapy.The nanosystem is constructed by co-encapsulation of UCNs,photosensitizer zinc phthalocyanine?Zn Pc?and antitumor drug doxorubicin inside the assembly of amphiphilic protein-polymer bioconjugate.The results show that UCNs successfully convert deeply penetrating near-infrared light to visible lights for simultaneous real-time fluorescence imaging and photodynamic therapy by activating Zn Pc to generate cytotoxic ROS.Compared with single PDT therapy or chemotherapy systems,the combination therapy UCNs system demonstrates significantly enhanced tumor cell killing efficiency.Finally,to overcome the spectral interference issues between coded signal and reporter signal in traditional downconversion materials-based immunoassays,upconverting nanocrystals encoded magnetic microspheres?UCNMMs?are successfully developed by incorporating UCNs and magnetic Fe₃O₄ nanoparticles into porous polystyrene microspheres.In UCNMMs-based immunoassays,UCNs and reporter signals are separately excited by near-infrared and UV/visible light.The results show that the UCNMMs possess a lot of advantages including photostable fluorescence,fast magnetic separation and sensitive detection without optical spectral interferences between the coded UCN signal and reporter dye signal.The UCNMMs have been successfully used for mouse Ig G with a detection limit value of 0.01 ng/m L.Taken together,we have successfully developed a serious of QDs and UCNs-based multifunctional nanoplatforms tumor diagnosis and therapy.All the results suggest that they have great potential in the field of tumor theranostics.