Preparation And Surface Control Of Functional Nanomaterials For The Optical Diagnosis And Therapy Of Cancer

The development of precision medicine provides an innovative insight and strategy for the clinical diagnosis and therapy of cancer.For its advantages of non-invasive and high-efficiency controllable model,the optical diagnosis and therapy provide a feasible approach for in situ cancer theranostic.Functional nanomaterials with excellent optical properties display wide potentials in applications of early diagnosis,interventional therapy and predicting prognosis of cancer.This dissertation investigates the approaches of preparation and surface control of functional nanomaterials,and fabricates the life-essential elements-based functional inorganic nanomaterials for the optical detection,imaging,and therapy of cancer.The as-prepared polymer-coated superparamagnetic iron oxide nanoparticles effectively extract the tumor-related viral nucleic acids,and are sequentially employed for the optical detection by real-time fluorescence quantitative polymerase chain reaction(RT-PCR).Afterwards,black phosphorus nanosheets with different surface chemical activities are fabricated via chemical coordination and surface oxidation.Multiple optical imaging approaches are utilized in exploring the surface chemical activity-relative intracellular degradation behavior,the mechanism of selective cell killing and the performance of cancer bioactive phosphorus-based therapy(BPT).Finally,the biophotonic silicon nanosheets are synthesized based on a facet-selective cleavage strategy method for the near-infrared Raman imaging-guided photothermal therapy(PTT)of cancer cells.1.Fabrication of magnetic nanoparticles for the optical detection of cancer-related virusThe continuous infection of virus is easy to the tumorigenesis in normal cells,and then results in the formation and development of cancer.Thus,sensitive detection of cancer-related virus can efficiently reveal early risks of related cancers.Herein,a platform of magnetic nanoparticles(MNPs)-based automated nucleic acid extraction is adopted to effectively capture virus nucleic acid,which is subsequently employed for highly sensitive detection by RT-PCR assays at low viral concentrations.Poly(amino ester)with multiple carboxyl groups(PC)are coated on the surface of MNPs by organic coating protocol.The carboxyl functional MNPs is devoted to capturing virus nucleic acid with high efficiency in various samples,and then achieving RT-PCR optical detection with high sensitivity and repeatability.Highly sensitive viral detection is achieved in serum samples with liver cancer-related hepatitis B virus(HBV),and cell samples with cervical cancer-related human papilloma virus(HPV)respectively.Benefitting from the simplicity and excellent performances,this method of MNPs-based optical detection is of great significance for the early risk monitoring of tumorigenesis.2.Evaluation of bioactive phosphorus-based therapy effect of black phosphorus nanosheets based on tumor optical imagingBioactive phosphorus-based therapy(BPT)as an alternative therapeutical strategy exhibits a great application prospect in cancer selective chemotherapy.Black phosphorus nanosheets(BPs)as a type of ideal bioactive material provides the option for the development of nano chemotherapeutic drugs.To explore the relationship of selective antitumor bioactivity and chemical activity,BPs with different surface features have been well-designed via surface control.Bared BPs formed by a liquid-phase exfoliation(LPE)method is developed for the fabrication of passivated BPs and oxidized BPs by chemical coordination and oxidation treatment respectively.The as-prepared three types of surface-active BPs exhibit different degradation behaviors in aqueous solution and physiological conditions.Raman imaging are employed for monitoring the intracellular degradation behaviors of BPs.Such surface chemical activity-relative degradation behaviors lead to selective and controllable cancer chemotherapeutic effects of BPs.BPT effects of BPs are assessed by in vivo fluorescence imaging the red fluorescent protein(RFP)-expressing tumor.Moreover,the mechanism of BPs-induced cell anti-proliferation and cytotoxic effects is analyzed by intracellular fluorescence imaging.The biological effects are resulted from BPs induced cell cycle arrest and subsequently programmed cell death including cell apoptosis,autophagy,and necroptosis.The surface chemical activity-relative growth suppression and eradication of tumor offer alternative perspectives for the development of other inorganic active nanomaterials.The strategy of evaluating antitumor performance based on optical imaging has effectively promoted the clinical applications of nano chemotherapy drugs.3.Fabrication of silicon nanosheets for the biological photo-therapy of cancerSilicon-based nanomaterials with excellent biocompatibility and biodegradability have been widely concerned in biomedical fields.For its unique biophotonic properties,two-dimensional(2D)silicon nanosheets(Si NSs)as a promising photo-functional material are applied in the optical diagnosis and therapy of cancer.To achieve large-scale preparation of Si NSs,the octahedron silicon crystals(oct-Si crystals)with the fully exposed {111} planes are synthesized based on the chemical vapor transport(CVT)method,and sequentially cleaved via LPE for the successive preparation of Si NSs.Upon near-infrared(NIR)irradiation(785 nm),Si NSs with robust Raman scattered signals are utilized for intracellular Raman imaging.Moreover,for the high photothermal conversion capability,Si NSs as a NIR-II(1064 nm)photothermal agent exhibit the high-effective killing properties of cancer cells.The model of NIR Raman imaging-guided photothermal therapy provides an effective strategy for cancer theranostic.The strategy of facet-selective cleavage provides a novel insight for the synthesis of 2D non-van der Waals(vd W)materials.