Preparation Of Fluorescent Carbon Dots And Their Performance In Bioimaging And Tumor Therapy

Cancer is a leading cause of death worldwide.According to the World Health Organization(WHO),nearly 10 million deaths from cancer will occur in 2020.Almost90% of these deaths are caused by metastasis,and cancer-related deaths are expected to increase to 270 million by 2050.Currently,the primary cancer treatment methods include surgery,radiotherapy,and systemic therapy(chemotherapy,hormone therapy,targeted biotherapy).Among them,the exclusive administration of drugs to solid tumors used to eliminate tumor cells is one of the main methods to prevent or hinder their growth.However,this method has multiple side effects,such as drug resistance,immune system imbalance,and complications caused by subsequent treatments,which seriously affect patients’ clinical cure and survival rates.In contrast,fluorescent nanomaterials have been widely used in bioimaging-guided tumor tracking therapy due to their unique surface functional groups,particle size,and structural features,which significantly improve clinical patient cure rates and survival rates.Carbon dots(CDs),a new type of 0-dimensional carbon nanomaterials,have received increasing attention in biosensing,drug/gene delivery,and tumor diagnosis and therapy due to their ultra-small size,easy surface doping,and inherent optical properties.Based on this,this paper utilizes doping elements to change the HOMO-LUMO energy gap or bandgap on which CDs depend to adjust the fluorescence color and quantum yield.Using organic small molecules and metal hydrochloride as precursors,a series of elementally doped CDs were designed and equipped for exploring their research in toxicology,bioimaging,and tumor therapy.The details are as follows: a series of elementally doped CDs were designed and prepared for exploring their research in the fields of toxicology,bioimaging and tumor therapy.The details are as follows:(1)NIR fluorescent Cu,N co-doped CDs with promising physicochemical properties and high quantum yield were obtained by solvothermal method through optimizing the reaction conditions.Compared with carbon black nanoparticles,Cu,N co-doped CDs had somewhat little effect on the contents of IRE1α,chop,and cleaved caspase-3/pro-caspase-3 content were relatively less affected,showing better biocompatibility and lower cytotoxicity.In addition,Cu,N co-doped CDs also exhibited better in vitro fluorescence imaging in human umbilical vein endothelial cells at optimal concentrations.(2)N-doped CDs with surfaces enriched with β-cyclodextrin functional groups were prepared by a solvothermal method.The effects of different β-cyclodextrin contents on the structural and optical properties of the synthesized CDs were investigated.The mechanism of the photoluminescence action of N-doped CDs was analyzed.Due to the excellent biocompatibility and color tunability of N-doped CDs,N-doped CDs showed bright and stable purple,blue,green,yellow,and red fluorescence in MCF-7 cells.Moreover,by optimizing the imaging conditions of N-doped CDs with mitochondria-specific dyes,purple,blue,and green mitochondria-targeting co-localization imaging of MCF-7 cells was also successfully achieved.However,during the exploration of different injection methods for in vivo fluorescence imaging in Balb/C tumor-bearing mice,it was found that tail vein injection of N-doped CDs was less effective in enrichment the tumor site in mice,and further optimization of the formulation of N-doped CDs is needed to improve the tumor-targeted imaging effect of N-doped CDs.(3)Three types of dual-emission fluorescent CDs,namely,P,W co-doped CDs,P,W,Hf co-doped CDs-1,and P,W,Hf co-doped CDs-2,were prepared using metal hydrochloride salt as a precursor doping material.The effects of doping with P,W,and Hf ions on the optical properties of the CDs were investigated.It was found that the presence of valence electrons in the metal ions could promote the electron transfer between the metal ions and the CDs,resulting in the formation of radiative electron complexes and holes on the surface of the CDs,thus enabling the obtained CDs to exhibit excellent physicochemical properties,high quantum yields,and ex vivo imaging potential.Moreover,by comparing the ex vivo imaging,biodistribution,and pharmacokinetics of the three CDs,it was found that P,W,Hf co-doped CDs-1 not only ensured their aggregation but also effective retention in the tumor region of Balb/C tumor-bearing mice,which showed unique advantages in ex vivo fluorescence/CT imaging and biosafety.(4)Bi-doped CDs with diagnostic and therapeutic potentials were prepared for the first time.Then,Bi-doped CDs functionalized liposomes(Lipo/Bi-doped CDs)were synthesized in a specific ratio with the help of the thin film hydration method.The in vivo and in vitro fluorescence imaging of Bi-doped CDs and Lipo/Bi-doped CDs were explored,and it was found that the Lipo/Bi-doped CDs could be visualized and traced by fluorescence imaging,and the rates of cellular uptake and drug release from liposomes at different p H were detected by bright and stable fluorescence signals.Meanwhile,due to the passive targeting and drug-loading properties of liposomes,the enrichment content of Bi-doped CDs in tumors was increased,which improved the fluorescence imaging and therapeutic effect of tumors.In addition,this good tumor treatment and fluorescence imaging effect can be verified by sufficient visualization time,which shows enormous potential in fluorescence imaging-guided tumor tracking and treatment.