Second Near-infrared Luminescent Probe Based On Rare Earth Nanoparticles:Fabrication And Their Applications

Cancer poses a great threat to human health.Therefore,there is an urgent need to develop efficient and low-cost nanoplatforms for cancer diagnosis and treatment.Common imaging modalities include magnetic resonance imaging and computed tomography,etc.However,their disadvantages are high cost,resolution and sensitivity are limited.In order to solve these problems,fluorescence imaging technology based on nano-optical materials has attracted great attention of researchers.So far,fluorescence imaging technology has been widely used in clinic because of its advantages of high spatial resolution and sensitivity.Current fluorescence imaging mainly focuses on the visible（400-650 nm）and near-infrared（NIR-I,700-900 nm）regions.However,the light in two regions has relatively large light scattering and tissue autofluorescence,which will affect the imaging quality.Fortunately,fluorescence imaging techniques based on the second near-infrared region（NIR-II,1000-1700 nm）have developed rapidly in recent years.NIR-II fluorescence imaging has the advantages of low light scattering loss and high tissue penetration depth,as well as high imaging resolution and signal-to-noise ratio,especially in the b region（NIR-IIb,1500-1700nm）in the second near-infrared window It is better reflected in imaging and has become a tumor imaging technology with great clinical application potential.In short,the development of NIR-II fluorescent probes based on high luminescence efficiency is particularly critical to improve the quality of NIR-II fluorescence imaging.In this paper,two NIR-II nano-fluorescent probes based on rare earth nanoparticles were fabricated and successfully applied to tumor-targeted NIR-II fluorescence imaging.1.A NIR-IIb fluorescent probe（DSNP@m Si O₂@ICG-TPP,DSI-TPP NPs）based on rare earth nanoparticles was fabricated.In this probe,the rare earth nanoparticles DSNPs were synthesized by solvothermal method.The NIR-IIb fluorescence imaging performance was effectively improved by rationally doping other rare earth elements in the rare earth element Y matrix to regulate its energy transfer pathway.Further,mesoporous silica（m Si O₂）was coated on the surface of DSNPs,and the absorption of DSNPs was sensitized by loading indocyanine green（ICG）in the hydrophobic channels of m Si O₂,which greatly enhanced the NIR-IIb fluorescence imaging performance.In addition,by covalently modifying the mitochondrial targeting agent（4-carboxybutyl）triphenylphosphine bromide（TPP）on the surface of m Si O₂,the probe has good biocompatibility and the function of targeting mitochondria.Due to the longer wavelength of light in the NIR-IIb region,the fluorescence imaging quality will be higher,and it can be better applied in tumor imaging.Therefore,experimental studies in vitro and in vivo have shown that the fluorescent probe can realize mitochondrial imaging,tumor and blood vessel NIR-IIb fluorescence imaging.2.A tumor microenvironment（TME）-responsive NIR-II fluorescent probe based on rare earth nanoparticles was fabricated.First,the rare earth downconversion nanoparticles（DCNPs）were combined with oxygen-deficient molybdenum oxide(Mo O_3-x)through amide bonds,and then the surface was coated with hyaluronic acid（HA）to finally preparate nanoprobe(DCNP-Mo O_3-x@HA,DM@HA).Therefore,the nanoprobe realized the function of TME-activated NIR-II fluorescence imaging.Besides,we improved the luminescence intensity of DCNPs by doping Ca²⁺ions and rare earth Gd³⁺ions,which also endowed the nanoprobe with magnetic resonance imaging performance.In this probe,due to the strong absorption of Mo O_3-x in the NIR-II region,the fluorescence of DCNPs can be quenched by fluorescence resonance energy transfer（FRET）process.When the nanoprobe was targeted to CD44-rich tumor sites through HA,the Mo O_3-x would be gradually degraded under the effect of TME overexpressing H₂O₂and blocked the FRET effect,thereby restoring the NIR-II fluorescence of DCNPs.Experimental studies have shown that the TME-responsive NIR-II fluorescent probe has great potential in tumor diagnosis.