Synthesis Of Ultrabright Silicon-containing Nanodots And Their Applications As Fluorescent Probes And Nanocarriers

Photoluminescent nanomaterials(PLNMs)have been extensively used in various biomedical fields such as biosensing,bioimaging,diagnostics,and therapy.Compared to organic fluorescent molecules,PLNMs have higher photostability and larger tunable emission wavelength range,and have thus gained much attention in recent years.Although various PLNMs including semiconductor quantum dots,metal nanoclusters,upconversion nanomaterials,polymer dots,graphene quantum dots,and carbon nanodots have been synthesized,their biomedical applications are usually limited because of many drawbacks such as potential cytotoxicity,low photoluminescence(PL)quantum efficiency,complicated synthetic procedures,broad PL emission peaks,poor water-dispersibility,difficulty of modification,and high cost.Therefore,it is urgently needed to develop new PLNMs with superior optical and biocompatible properties to overcome the above-mentioned shortcomings.Fluorescent silicon-based nanodots(SiNDs),as a typical class of zero-dimensional silicon-containing nanomaterials,have potential biomedical applications due to their superior characteristics including favourable optical properties,facile surface functionalization,and minimal toxicity.However,developing a simple strategy for the preparation of water-dispersible SiNDs whose fluorescence properties can be comparable to those of the II-VI semiconductor quantum dots remains a challenging task.In this thesis,green-emitting organosilica nanodots(OSiNDs)are sythesized with photoluminescence quantum yields(PLQYs)up to ~100%,narrow PL bandwidths(full width at half maximum(FWHM)? 30 nm),and excellent biocompatibility.The OSiNDs can realize long-time lysosomal imaging with washing-,fixation-,and permeabilization-tolerant capability.Besides,compared with commercial lysosomal imaging reagents(LysoTracker Green and LysoTracker Red),the OSiNDs have better lysosomal specificity and higher photostability,which makes them promising candidates as novel lysosomal trackers.On the other hand,the OSiNDs can be a general fluorescent probe for live/dead discrimination of bacterial,fungal,and mammalian cells.With their superior photostability and low cytotoxicity,the OSiNDs address the shortcomings of the existing commercial reagents(SYTO X and propidium iodide)and will meet the demand of green-emitting probes for labeling dead cells.Meanwhile,by combining a commercial red-fluorescent dye SYTO 60 and OSiNDs,we develop a method for rapid and accurate quantification of live/dead cells.Besides,taking doxorubicin(Dox)as a model drug,we realize the real-time and in situ evaluation of the toxicity/efficacy of Dox in vivo by using the green-fluorescent OSiNDs with high sensitivity to cell viability.In addition,a new class of epoxy group-terminated OSiNDs is prepared and employed as a multifunctional platform for imaging and eliminating multidrug-resistant bacteria(MRB)as well as their biofilms.Using one-step hydrothermal reaction of an epoxy group-containing silane molecule,3-glycidoxypropyltrimethoxysilane(GPTMS),and an organic dye,rose bengal,green-emitting OSiNDs are obtained with several unique properties including a high fluorescence quantum yield of 31% for imaging,the ultrasmall size for entry into bacteria,the proper surface chemistry(with epoxy groups)for improving the affinity for bacteria,and the negative surface potential endowing the nanodots with the ability to escape from the efflux proteins/intracellular enzymes of MRB and to avoid being detained by the extracellular polymeric substances matrix of bacterial biofilms,thus promoting the penetration of OSiNDs into biofilms.Based on these properties,the OSiNDs realize universal imaging of various types of bacteria(including Gram-negative,Gram-positive,and drug-resistant bacteria)and the corresponding bacterial biofilms,thus providing information such as the bacterial density/distribution in biofilms and biofilm thickness for the treatment of bacterial infections.On the other hand,using a highly efficient reaction between the amine groups of vancomycin(Van)and the epoxy groups of OSiNDs,we successfully prepare Van-loaded nanodots(termed OSiNDs-Van).The OSiNDs-Van are able to efficiently inhibit the growth of the MRB and even significantly destroy the biofilms of MRB.Collectively,such a strategy to construct multifunctional nanoplatforms using biocompatible silicon-containing nanodots for imaging and eliminating MRB and their biofilms will offer a new idea to overcome the drug resistance of bacteria.In summary,this thesis improves the fluorescence and surface chemistry properties of silicon-based nanodots,broadens their biomedical applications,and provides new solutions for the development of new silicon-based fluorescent probes and drug carriers.