Multifunctional Nanomaterials For Near-infrared Molecular Imaging And Tumor Visualized Precision Combination Therapy

It is well known that early diagnosis and precise treatment of major diseases,especially tumors,is crucial to improving the cure rate and the quality of life of patients.Therefore,the development of high-precision,sophisticated diagnostic techniques and efficient,non-toxic treatments are the main goals of modern medicine.The rapid development of molecular and nano imaging plays an increasingly important role in early diagnosis of diseases and real-time evaluation of therapeutic effects.The combination of different therapies and immunotherapy in recent years has greatly improved the effectiveness of cancer treatment.Nanoparticles could integrate different diagnostic techniques and therapeutic methods,and it could enter deep into tumor tissue through high permeability and high retention effect(EPR effect).Thus,nanoparticles are widely used in cancer diagnosis and treatment.In this paper,we broadened near-infrared fluorescence imaging 900 – 1,000 nm(NIR-Ib)windows scope and applied it to NIR-Ib fluorescence imaging-guided photothermal therapy in glioma.Then,we explored the combination of phototherapy and immunotherapy / chemotherapy,which have provided new ideas and new methods for the diagnosis and treatment of tumors.The main contents are as follows:(1)Near-infrared fluorescence imaging in the window of 900 – 1,000 nmThe traditional near-infrared fluorescence imaging view is that the 900 – 1,000 nm(NIR-1b)windows are an optically opaque region because there have a water absorption peak and few fluoroprobes in the NIR-Ib region.We found that some heptamethine cyanine dyes had different fluorescence emission peaks not only in the 700-900 nm(NIR-Ia)region and NIR-1b region.As these dyes entered plant leaves and tumor-bearing mice,we clearly observed the veins,infected anthrax location,lymphatic vessels,brain tumors and subcutaneous tumors though NIR-1b fluorescence imaging.Compared to conventional NIR-Ia fluorescence imaging,NIR-Ib images had higher signal-to-noise ratio because autofluorescence,scattering and light absorption of biological tissues and water significantly reduced at longer wavelengths.These findings challenge scientists' current view of the near-infrared fluorescence imaging spectral scope,and the development of NIR-Ib fluorescence imaging technology will be important for biomedical research.(2)Macrophage membrane camouflage nanoparticles for NIR-Ib fluorescence imaging-guided photothermal therapy in the gliomaWe designed that macrophage membrane coated liposomes loading IR-792 with NIR-Ib fluorescence and photothermal function nanoparticles(MDINPs).MDINPs with strong fluorescence stability and high photothermal conversion efficiency could penetrate the blood-brain barrier(BBB)and accumulated tumors.Gliomas were clearly observed by MDINPs-mediated NIR-Ib fluorescence imaging.In addition,NIR-Ib fluorescence imaging-guided photothermal therapy in glioma significantly inhibited the growth of gliomas.This work provided a new method for the integration of diagnosis and treatment of glioma.(3)PDT-enhanced cell-membranes immunotherapy based on NK cell membrane-decorated nanoparticles effectively inhibits primary and distal tumor growthNK cell-membrans-decorated polymer-loaded photosensitizer TCPP nanoparticles(NK-NPs)have developed a novel cell-membranes immunotherapeutic strategy.The proteomics of NK cell-membranes were analyzed,and it was found that NK cell-membranes(NKCMs)were capable of targeting NK-NPs to tumors and could induce or enhance M1-macrophage polarization to generate antitumor immunity.The TCPP loaded in NK-NPs could induce dying tumor cells to produce damage-related molecules patterns by PDT,and thus enhanced the antitumor immunity efficiency of NKCMs.NK-NPs selectively accumulated in tumors and were capable of eliminating primary tumor growth and generating an abscopal immune effect that inhibited distant tumor growth.This work provided new ideas for tumor immunotherapy.(4)The application of albumin-loaded indocyanine green and selenium nanoparticles in the combined treatment of photothermal therapy and chemotherapyWe developed bovine serum albumin co-loaded with nano-selenium(SeNPs)/ indocyanine green(ICG)nanoparticles(BSINPs)for the combined potothermal therapy and chemotherapy of tumor.BSINPs exhibited good monodispersity and photothermal stability.In addition,BSINPs had longer retention time at tumor and high photothernal conversion efficiency under laser irradiation.BSINPs-mediated photothermal-chemo therapy completely inhibited the growth of glioma and no tumor recurrence was observed compared with photothermal therapy or chemotherapy alone.BSINPs-mediated photothermal-chemo therapy provided new measures for cancer treatment.Multifunctional nanoparticles could integrate different diagnostic techniques and therapeutic methods,and the long-term circulation,targeting and controlled release of nanocarrier system successfully overcome the low bioavailability,poor stability and short half-life of the existing antitumor drugs.With the development of nanotechnology,new diagnostic technologies and nanomedicine based on nanomaterial bring hope to cancer diagnosis and treatment.