Study Of Boron Nitride Nanospheres As An Efficient Anticancer Drug Delivery Vehicle

With its unique physical and chemical properties and structural similarity to carbon,boron nitride(BN)has attracted considerable attention and found many applications.Biomedical applications of BN have recently started to emerge,raising great hope in drug and gene delivery.At present,this application was primarily based on boron nitride nanotube(BNNT),while the biomadical use of boron nitride nanospheres(BNNS)with uniform spherical structure was rarely reported.Research has shown that the spherical particles are more suitable as drug delivery vehicles due to their ingestible and injectable properties.It is of great significance to investigate the biosafety and drug delivery behavior of BNNS.In this work,base on their excellent properties,BNNS with different functionalized modification were fabricated to study their potential applications in anti-tumor drug delivery and treatmen.The main contents include the following sections:Chapter 1: The structure,fabrication,main properties and applications of boron nitride nanomaterials were reviewed in this chapter.Then,the research progress of boron nitride in the field of biomedicine was briefly introduced.Moreover,the problems existing in the application of boron nitride in biomedical field such as hydrophobic and lack of target,as well as the functional modification methods of boron nitride were briefly introduced.In summary,combined with the application potential of BNNS in anti-tumor drug delivery and treatment,the basis of the topic and the target of this thesis were given.Chapter 2: A novel targeted anticancer drug delivery system BNNS-FA complexes were fabricated by covalent functionalization of FA onto BNNS via esterification reaction.BNNS-FA complexes were nontoxic to HeLa cells.Then,the cellular uptake of the BNNS-FA complexes was further investigated,the results confrmed the enhanced internalization of BNNS-FA complexes by FR-mediated endocytosis pathway.Meanwhile,doxorubicin(DOX),a model of anticancer drug,was loaded onto BNNS-FA complexes and the cytotoxicity of BNNS-FA/DOX complexes against HeLa cells was confirmed.The potential application of BNNS as carriers in cancer therapy was firstly validate by this work.Chapter 3: In this chapter,a targeted anticancer drug delivery system with core–shell structure(BNMS-FA)was fabricated based on mesoporous silica(MS)coating and FA modification.The modification of MS helped to improve drug loading capacity and dispersity of BNMS-FA complexes.After DOX loadig,in vitro cytotoxicity of BNMS-FA/DOX complexes against cancer cells were verified.Chapter 4: A pH-responsive charge-reversal polyelectrolyte(PAH-cit)functionalized BNNS complex was fabricated by self assembly.The drug release behavior of DOX@PAH-cit/BNNS in HeLa cells and different pH buffer revealed that the loaded drug could be effectively released from the complexes at acidic pH condition.Finally,HeLa cells and MCF-7 cells were used to confirm the therapeutic efficiency of DOX@PAH-cit/BNNS complexes.Chapter 5: Red blood cell membrane coating technique was used to camouflage inorganic BNNS,thus forming biomimetic RBC-membrane-coated BNNS(RBC-BNNS)drug delivery system.This modification strategy firstly realized the monodispersity of hydrophobic inorganic nanomaterial BNNS in solution.The RBC-BNNS complex had superior biocompatibility and its DOX load capacity was much higher than that of BNNS.In addition,in vitro cytotoxicity assay preliminarily verified that DOX@RBC-BNNS has a more significant inhibition effect on cancer cells than free DOX.