Construction Of Multifunctional Organic Probes/Nanomaterials And Their Applications In Biological Detection And Tumor Therapy

Advanced optical technology mainly includes advanced laser and optical devices,whose application in the field of biology has promoted the development of modern medicine.They are capable of in situ high-resolution imaging of cells or living organisms,providing a powerful tool for revealing the pathogenesis and signaling pathways of diseases.Since many diseases are easier to cure in the early stage than in the late stage,the development of early diagnosis technology is of great significance to improve the survival rate and quality of life of patients.Understanding the interactions of multiple chemical substances in the cellular pathway,their distribution in the cells,and the differences in the concentration distribution of the same substance in different parts of the tissue can help solve most biological problems.Therefore,it is of great significance to develop multifunctional probes that can achieve quantitative detection or simultaneously image multiple substances.In addition,various laser medical devices show great potential in treating various diseases such as tumors.Phototherapy has significant advantages in precision medicine due to its noninvasive and excellent spatiotemporal selectivity.However,due to the characteristics of tumor recurrence and metastasis,single-function phototherapy is not sufficient in the treatment of persistent tumors.There is an urgent need to develop multifunctional nanomaterials to realize the combination of tumor therapy.Based on the above problems,the researches carried out in this paper are as follows:1.Pd NPs/CMC-COF-LZU1 was constructed via in situ growth of palladium nanoparticles（Pd NPs）in aqueous stable carboxymethyl cellulose modified covalent organic frameworks（COFs）.Encapsulation of Pd NPs in COFs can improve its catalytic activity and stability,while cellulose modification can improve the dispersion of COFs in aqueous solution.The resulting nanocomposite has been proven to have a superior catalytic performance for the transformation of N-butyl-4-NHAlloc-1,8-naphthalimide（NNPH）into N-butyl-4-amido-1,8-naphthalimide（NPH）,resulting in significant changes in both color and fluorescence.Pd NPs/CMC-COF-LZU1 also showed good catalytic properties for NNPH in He La cells,achieving precise and sensitive colorimetric detection and multi-color imaging of cancer cells.COF-based composite materials（Pd NPs/CMC-COF-LZU1）have tremendous potential applications in biotechnology and biological science.2.A ratiometric fluorescent probe with high fluorescence quantum yield in a highly polar environment was synthesized to reveal polarity abnormalities in Alzheimer’s disease（AD）.The strong donor-acceptor electron pair in the conventional dye Cy7-Cl was broken to obtain a polar-sensitive ratiometric fluorescent probe HCy7-K.Cell imaging showed that the probe could image the polarity changes of lipopolysaccharide（LPS）-induced inflammation in nerve cells.Such ratiometric fluorescent probes of neutral molecules have great potential for the study of AD and other brain-related diseases.3.A multifunctional fluorescent probe（AD-3）based on 1,8-naphthimide and rhodamine fluorescent skeletons was constructed for simultaneous imaging of H₂S and adenosine triphosphate（ATP）in HT22 cells and Alzheimer’s disease mouse brain.AD-3 showed good linear correlation and low detection limit with both H₂S and ATP in vitro.Cell imaging revealed a synergistic relationship between ATP and H₂S.Real-time quantitative reverse transcription polymerase chain reaction（RT-q PCR）and Western blot assay（WB）confirmed that H₂S regulates ATP synthesis by acting on cytochrome C of complex III,cytochrome oxidase subunit 3 of complex IV,and protein 6 of complex I of the mitochondrial respiratory chain.Subsequently,AD-3 was used to construct an HTS platform to directly perform high-throughput screening of anti-AD drugs by observing changes in intracellular H₂S and ATP levels.4.Here,we first reported a coordination assembled strategy for synthesis of Cu（II）-flavone coordination polymer prodrug（NCu-Fle CP）.NCu-Fle CP is stable under normal physiological conditions,but reduces to small size prodrug complex and releases CO and·OH on demand under Glutathione（GSH）,H₂O₂ and near infrared（NIR）light in the tumor.Detailed in vitro and in vivo experiments have shown that NCu-Fle CP can produce sufficient amounts of CO and·OH within cancer cells and has significant destructive effects on cancer cells without toxicity to surrounding normal tissues.Our study provides a solid foundation to develop smart coordination polymer CO prodrugs with on-demand CO release and biodegradability for multimodal synergistic therapy.