Fabrication Of Water-Dispersed All-Inorganic Perovskite-Based Fluorescent Probes And Their Application In Tumor Marker Recognition

All-inorganic perovskite nanocrystals have been applied in many optoelectronic fields due to their high photoluminescence quantum yield,a wide range of excitation spectrum,narrow emission bands,and tunable emission wavelength covering the entire visible spectral region.However,there are still many factors limiting the biological applications of all-inorganic perovskite nanocrystals:（Ⅰ）the rapid hydrolysis in aqueous and oxygen environments;（Ⅱ）the fluorescence quenching may easily appear in the biological modification process;（Ⅲ）bio-toxicity,etc.In this work,water-dispersed all-inorganic perovskite nanocrystals were synthesized,which were used as targeting probes for tumor cells after surface modification.By using polymer materials as a protective layer or combining with metal nanoprobes,a variety of water-dispersed all-inorganic perovskite fluorescent nanoprobes were constructed.In addition,the optical properties of water-dispersed all-inorganic perovskite-based fluorescent nanoprobes were explored.Further,the recognition of tumor markers was realized by using such nanoprobes,which provided a novel way for developing the application of all-inorganic perovskite nanocrystals in the biological field.The main innovative results of the thesis are summarized as follows:（1）A phospholipid-assisted water-dispersed all-inorganic perovskite nanocrystal was constructed.All-inorganic perovskite-phospholipid micelle nanoprobes were obtained by encapsulating oil-phase all-inorganic perovskite nanocrystal into the amphiphilic phospholipids,which kept the excellent fluorescence properties of all-inorganic perovskite nanocrystals and achieved superior stability in an aqueous solution for more than four months.Such an all-inorganic perovskite-phospholipid micelle can be internalized by He La cells rapidly and is enabled to realize multicolor imaging.Further,He La cells were identified by folate-modified all-inorganic perovskite-phospholipid micelles.The experimental results in vitro and in vivo verified that the toxicity of all-inorganic perovskite-phospholipid micelle nanoprobes was significantly reduced after embedding all-inorganic perovskite nanocrystals into micelles.Furthermore,the targeted imaging of SKBR3 cells and the optical sensing of SKBR3 cell-derived exosomes were achieved by combining all-inorganic perovskite-phospholipid micelles with Au@Ag nanoprobes.（2）A water-dispersed all-inorganic perovskite nanocrystal was proposed as a super-resolution fluorescence nanoprobe,which realized an～3 nm localization precision.In the super-resolution image,two closely spaced all-inorganic perovskite nanocrystals with a gap of40 nm can be clearly distinguished.Meanwhile,the size of all-inorganic perovskite nanocrystals labeled cell-derived exosomes in super-resolution images was consistent with the actual size of exosomes（30-150 nm in diameter）.Further,after being functionalized by biotin,the super-resolution images of both nuclear lamina and cell membranes with an enhanced resolution were achieved by all-inorganic perovskite-based targeted nanoprobes,which may open up a new avenue for the application of perovskite nanocrystals in tumor markers super-resolution imaging.（3）A new method to tune the emission wavelength of water dispersed all-inorganic perovskite nanocrystals was proposed.By one-step method to encapsulate hydrophilic all-inorganic perovskite nanocrystals into polyethylene glycol-（amine）₂（HCl salt）,a wavelength-tunable all-inorganic perovskite-based fluorescent nanoprobe was obtained with a narrow FWHM as 11 nm and an accurate localization precision as sub-10 nm.Such a nanoprobe had a broad spectral tunability from 431 to 521 nm,superior photostability for more than 20 months,and surface-functionalized ability,which exhibited a bright prospect in the field of color encoded.In the experiments,all-inorganic perovskite-based fluorescent nanoprobe realized non-specific super-resolution imaging of cancer cells-derived exosomes and specific super-resolution imaging of HER2 receptor protein on the surface of cancer cells due to high localization precision.Further,the narrow FWHM of all-inorganic perovskite-based nanoprobe is beneficial to achieve multicolor super-resolution imaging of different objectives.