Design,Synthesis And Biomedical Application Of Carbon-Based Nanomaterials

Although metal-based or semiconductor-based nano-reagents have demonstrated great potential as cancer therapeutic agents,the off-target side effects and the difficulty in metabolizing remain issues to be addressed.This study focused on the exploration practices for carbon-based nano-reagents with more secure and metabolizable in tumor models.From the perspectives of nanomaterial design and synthesis,the regulate and control of organic solvents as the main line,we synthesized carbon-based nano drugs with excellent tumor inhibition potential,and systematically explored their multi functions such as stimulation response,diagnostic imaging,biological safety and other functions.Then we further explored their application in variable tumor treatment modes based on their unique structural and functional characteristics.The chapter two demonstrates that graphene quantum dots(GQDs)with obvious optical absorption(1070 nm)in the second near-infrared window were prepared for the first time,and the potential of GQDs aimed to photothermal therapy(PTT)was evaluated in a mouse breast cancer tumor bearing model.As a paradigm,9T-GQDs containing of only C and O elements were successfully prepared by regulating the degradation of organic molecules,dissolved oxygen content and free radical life in acetone by external magnetic field.9T-GQDs exhibit a small size distribution(～3.6 nm),rapid metabolism ability(ti/2=1.59 h),excellent biocompatibility,and negligible systemic toxicity.The large conjugated system and high defect degree endow 9T-GQDs with excellent photothermal conversion efficiency(33.45%).Tumor growth in mice treated with single tail vein injection of 9T-GQDs and single 1064 nm laser irradiation,were significantly inhibited with a high tumor inhibition rate of 89.59%.In addition,the fluorescence quantum yield of 16.67%enables 9T-GQDs to illuminate tumor sites under laser excitation for real-time monitoring of tumor treatment process.This chapter promises that GQDs have great potential as secure and efficient reagents for tumor theranostics.Based on the solvent thermal synthesis route in chapter 2,we investigated whether solvents participate in the reaction under high temperature and pressure,and illustrates the structure-stability relationship of organic solvents in carbonization process in the chapter three.Nine kinds of common organic solvents as carbon sources(ethylene glycol,acetone,toluene,dimethylformamide,glycerol,ethylenediamine,methanol,ethanol,and carbon tetrachloride)were selected as models to investigate their direct decomposition and carbonization.Methanol,ethanol,and carbon tetrachloride exhibited excellent chemical stability,and the other six organic solvents undergo condensation,decomposition,and carbonization at high temperature to form fluorescent nanomaterials GQDs without the use of any catalyst or the introduction of other molecular precursors.The structure-stability relationship of organic solvents in the process of high-temperature carbonization is proposed.That is,organic solvents with single group or non-conjugated structure have excellent stability;organic solvents with double bond,or a benzene ring or double hydrophilic groups are unstable at high temperatures and can form carbon-based nanomaterials.This work provides guidance for solvent selection,optical origin of luminescent nanomaterials and surface modification in solvothermal synthesis at molecular level.The chapter four proclaims that metal-free multifunctional nanocarrier of graphitic carbon nitride quantum dots embedded in carbon nanosheets(CNQD-CN)was obtained via one-pot approach,and their photo-chemotherapy performance for oncotherapy was investigated in the cervical cancer tumor model in vivo.Based on the structure-stability relationship of organic solvents in the carbonization process in the chapter three,CNQD-CN was in situ synthesized by one-pot solvothermal treatment using formamide as a single source with neither additional catalysts nor other molecule precursors.CNQD-CN exhibits a shorter half-life constant(～1.64 h),tunable fluorescence properties and high biocompatibility.The CNQD-CN not only serves as an excellent NIR fluorescent marker,but also acts as a pH-/near-infrared-dual response responsive nanocarrier.Moreover,the CNQD-CN possesses both light-to-heat conversion and singlet oxygen generation capabilities under a single NIR excitation wavelength.Further investigations show that systemic delivery of doxorubicin using the multifunctional CNQD-CN nanocarrier under NIR irradiation was highly effective to cause cancer cell apoptosis in vitro and inhibit tumor growth(94.68%)in vivo.CNQDCN represents a multifunctional therapeutic platform for synchronous cancer imaging and treatment through the synergistic effect of phototherapy and chemotherapy.The chapter five proposes a "solvent self-carbonization-reduction strategy" for preparing ultrahigh density Cu single atom enzymes(SAEs)and the cascade catalytic ability of Cu SAEs for tumor elimination was investigated in a mouse breast cancer tumor bearing model.Based on the discover of that carbon-based fragments with reducing effects were produced in the carbonization and pyrolysis of formamide in chapter 4,CuⅠ SAEs were obtained by self-carbonization and reduction of organic solvents and CuⅡ salts.An unprecedented sequential catalytic performance for glutathione depletion and subsequent amplified hydroxyl radical generation was performed on the obtained CuⅠ SAEs with an ultrahigh density of 2.19 atoms/nm2(23.36 wt.%),in which the CuⅠ species serve as the active sites.The subversion of the homeostasis of the tumor microenvironment brought about by the Cu SAEs produces efficient ferroptosis and apoptosis in cancer cells,resulting in a high tumor inhibition rate of 89.17%.This study provides a novel strategy for fabricating SAEs supported on C3N4 for catalytic applications.