Research On The Construction Of Multifunctional Nano System And Its Application In Tumor Diagnosis And Treatment

Nanotheranostics,which can provide great insight into cancer therapy,has been deemed as a promising technology to settle the unmet medical needs.Compared with traditional imaging technology,fluorescence imaging technology has the advantages of high sensitivity,rapid and real-time monitoring,and has become the main technical means for exploring biological information in cells or tissues.Early fluorescence imaging research mainly focused on NIR-I(750-900 nm)in the near-infrared region.However,the strong fluorescence emission of biological tissues in this optical region results in low signal-to-noise ratio during imaging,which brings difficulties to tissue imaging and in vivo imaging in this wavelength range.NIR-II(1000-1700 nm)fluorescence imaging technology uses longer wavelength fluorescence to reduce the light scattering and absorption of the tissue,greatly reducing the background signal-to-noise ratio,and has a deeper tissue penetration depth and higher contrast,which better achieve biological tissue imaging.In recent years,new NIR-II fluorescent materials such as rare earth fluorescent materials,metal quantum dots,single-walled carbon nanotubes,and organic small molecules/polymers have been developed.Although inorganic materials have high fluorescence quantum yield and photothermal conversion efficiency,they are potentially toxic and have poor biocompatibility,which limits their clinical applications.In contrast,organic materials have good biocompatibility,optical stability,and high light-to-heat conversion efficiency,and have become a hot spot in the research of optical diagnostic and therapeutic agents.Photothermal/photodynamic therapy has high selectivity and low harm,and is developing into a new type of cancer treatment technology.This article proposes two new ideas for the construction and application of new nano-diagnostic reagents in the near-infrared zone.The specific contents are as follows:(1)Rational design of high performance nanotheranostics for NIR-II fluorescence/magnetic resonance imaging guided enhanced phototherapy:Through reasonable design and simple manufacturing,a universal nano-diagnostic agent DPPB-Gd-I NPs was constructed for dual-mode NIR-II/MR imaging-guided enhanced phototherapy.The obtained NPs showed outstanding biocompatibility,excellent NIR-II emission and NIR-I absorption,and excellent MR contrast function.Due to enhanced photodynamic therapy and enhanced photothermal therapy,this nano-agent can effectively destroy tumors under the conditions of single-dose injection and single NIR laser irradiation(tumor inhibition rate is as high as 94.5%).In addition,these nanoagents can be used as dual-mode NIR-II fluorescence/magnetic resonance imaging probes for tumor diagnosis,with high sensitivity,deep tissue penetration and excellent spatial resolution.In general,this work provides a powerful strategy for the development of high-performance nano-diagnostic and therapeutic agents for clinical applications.(2)Design and application of new organic small molecule NIR-II dyes:A new type of small molecule organic fluorescent material DPP-4NH₂ was synthesized.Through a simple nanoprecipitation method,DPP-4NH₂ NPs with good biocompatibility were obtained.The nanoparticle has good biocompatibility and rapid metabolic degradation.It also has good ultraviolet absorption capacity in NIR-I,and excellent NIR-II fluorescence emission.Besides,the nanoparticles have good photothermal performance and photodynamic performance,the photothermal conversion efficiency is 40.17%,and the singlet oxygen production rate(ROS)is as high as 34.26%.In the in vitro cell experiment,it showed a good inhibition rate on tumor cells.At the same time,the nanoparticles can be used for NIR-II fluorescence imaging,opening up a new field for single-wavelength excitation of NIR-II fluorescence imaging-guided phototherapy.