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Internalisation and trafficking of polymeric micelles in 2D and 3D cellular models in vitro
2018-08-22 12:05:13 | 【 【打印】【关闭】

SEMINAR 

  Biomaterials and Tissue Engineering Research Center, Shanghai Institute of Ceramics, Chinese Academy of Sciences 

  中国科学院上海硅酸盐研究所生物材料与组织工程研究中心 

    

  Internalisation and trafficking of polymeric micelles in 2D and 3D cellular models in vitro 

    

  报告人:Dr. Hongxu Lu 

  (University of New South Wales, Australia) 

    

    

  报告时间:2018827日(星期 一)下午1:30 

  报告地点:4号楼14楼第一会议室 

  联系人:吴成铁(52412249 

    

  欢迎广大科研人员和研究生参加! 

    

 

  Personal information: 

  吕宏旭博士现任澳大利亚新南威尔士大学化学系DECRA研究员。吕宏旭于20026月及20061月分别在中国海洋大学获得生物学理学学士及理学硕士学位,并于20094月在日本筑波大学获得工学博士学位(生物材料)。此后在日本国立物质材料研究所(2009年至2012年)及澳大利亚新南威尔士大学(2012年至2015年)从事博士后研究工作。2015年,获得澳大利亚研究理事会(Australian Research Council, ARC)优秀青年基金(Discovery Early Career Researcher Award, DECRA; 澳币35万,约合人民币180万),并被澳大利亚新南威尔士大学化学系聘为优秀青年研究员(DECRA Fellow)。     

  吕宏旭博士在细胞-纳米药物载体相互作用、细胞-生物材料相互作用及组织工程和再生医疗领域具有丰富的科研经验在日本攻读博士及博士后期间,师从国际著名生物材料及组织工程专家陈国平(Guoping Chen)教授,首次研发了自体同源的细胞外基质3D支架材料,并应用到了皮肤,软骨及骨的组织工程及再生医疗中。其开发的漏斗样孔隙复合支架材料具有独特的3D结构,可以促进细胞吸附及生长,已被证明可用于软骨及皮肤的再生。在新南威尔士大学工作期间,吕宏旭博士加入澳大利亚著名高分子及纳米材料专家MartinaStenzel教授课题组,利用新型的图案化2D细胞及3D多细胞模型,研究并探索了多种纳米粒子在细胞内的运输, 释放以及传递过程,并成功利用纳米粒子运输金属来抑制癌细胞迁移。目前已在SmallBiomaterials, Acta Biomaterialia, Biomacromolecules等权威期刊发表SCI论文72篇,论文总引1900余次,H指数25Google Scholar Citations)。已获得2项日本专利授权,并获得过2010台湾国际再生医疗材料大会优秀青年研究者奖和2012日本再生医疗学会优秀青年科学家奖。吕宏旭博士已做25次国际学术会议报告。201410月在海南举办的国际材联第二届国际青年先进材料大会中,共同组织了生物材料分会并应邀作报告。20155月被邀请至台北参加台湾-澳大利亚生物材料研讨会,并做邀请报告。吕宏旭博士目前担任澳大利亚研究理事会(Australian Research Council, ARC)优秀青年项目(DECRA), 探索项目(Discovery Projects)及联合项目(Linkage Projects)评委,也长期担任国际著名期刊Acta Biomaterialia, Journal of Materials Chemistry B, Biomaterials, Tissue engineering等的审稿人。 

    

  Abstract: 

  Polymeric micelles have been widely used as promising drug carriers for cancer therapy. Owing to the nano-scaled dimension and enhanced permeability retention (EPR) effect, polymeric micelles have prolonged circulation time and tend to accumulate in solid tumours. In addition, via the surface modification with active targeting groups and advances in development of stimuli-responsibilities, polymer micelles as drug carriers can overcome the limitations of traditional chemotherapy. In our lab, doxorubicin encapsulated polymeric micelles, ruthenium-drug encapsulated micelles, and glycopolymeric micelles were prepared, and these micelles have shown effective anti-cancer effects in vitro.       

  Cancers still pose a significant challenge to nanomedicine treatment because internalisation and trafficking of nanoparticles including polymeric micelles are not fully understood. In this study, both 2D and 3D in vitro cellular models were used to elucidate the nano-bio interactions. Native tumours are composed by heterogenous cells with different spreading, morphology, and metabolism et al. The change of cell spreading changes cytoskeleton arrangement. Thus, cell behaviours including adhesion, proliferation, and endocytosis are influenced by modifying cell spreading. It is hypothesised that the cellular uptake of nanoparticles via endocytosis will be influenced by changing cell spreading. Cancer cells and normal cells, including AsPC-1 cells, MCF-7 cells, A549 cells, umbilical vein endothelial cells (HUVEC) and mesenchymal stromal cells (MSCs) were cultured on micro-patterned surfaces, formed by immobilising photo-reactive polyvinyl alcohol on cell culture surfaces through photolithography process. The micro-patterns were used to control cell adhesion in order to force the cells to alter their spreading and internal cytoskeleton. The uptake of polymeric micelles of the cells on micro-patterned surfaces were investigated. It was found that cell spreading have significant influences on the internalisation of polymeric micelles.    

  Multicellular tumor spheroids (MCTS) exhibit higher similarity to in vivo tumour tissues than monolayer cells, and therefore are considered as the first choice of tumour models to bridge the gap between 2D monolayer in vitro results and in vivo tests. Interactions between nanoparticles and MCTS and the underlying mechanisms remain largely unknown. In our lab, MCTS were treated with various micelles and the penetration, drug delivery, anti-tumor and anti-metastasis effects were investigated. It was found that the penetration of polymeric micelles depends more on transcellular transport than on diffusion through ECM network between the cells. Stabilization via shell crosslinking improved the drug delivery efficiency of micelles in MCTS. It was also found that SPARC protein plays an important role in this penetration of albumin-based nanoparticles.    

  In summary, nanoparticles such as polymeric micelles hold great potential as drug carriers for cancer therapy, and the information on nano-bio interactions obtained with in vitro 2D and 3D models will be valuable for nanomedicine development.  

    

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