Mixed-Charge,pH-Responsive Nanoparticles for Selective Interactions with Cells,Organelles,and Bacteria  

作　　者：Marta Siek Kristiana Kandere-Grzybowska Bartosz A.Grzybowski 

机构地区：[1]Center for Soft and Living Matter,Institute for Basic Science(IBS),Ulsan 44919,Republic of Korea [2]Department of Biomedical Engineering,Ulsan National Institute of Science and Technology(UNIST),Ulsan 44919,Republic of Korea

出　　处：《Accounts of Materials Research》2020年第3期188-200,共13页材料研究述评（英文）

基　　金：This work was supported by the Institute of Basic Science,Republic of Korea(award no.IBS-R020-D1 to B.A.G.).

摘　　要：CONSPECTUS:Charged interfaces are ubiquitous in biology,from proteins,to membranes enclosing cells and organelles,to bacterial cell walls.For nanomaterials to interact with these biological entities effectively and selectively,their electrostatic properties must be fine-tuned.To date,charged nanomaterials have had their surfaces decorated with a single type of charged ligands(positive,negative,or zwitterionic),sometimes“diluted”with additional uncharged/hydrophobic ligands.Although such materials have shown some promise,they can be nonselectively cytotoxic or membrane-permeable,and can nonspecifically adsorb serum proteins or display limited cellular uptake.In this Account,we review a decade of our work on pH-responsive nanoparticles(NPs)covered with mixtures of oppositely charged ligands.These so-called mixed-charge nanoparticles(MCNPs)comprise d∼4−12 nm Au cores protected with mixed monolayers comprising positively charged N,N,N-trimethyl(11-mercaptoundecyl)ammonium chloride(TMA,[+])and negatively charged mercaptoundecanoic acid(MUA,[−])ligands at varying and precisely adjustable proportions.The MCNPs are pH-responsive because MUA ligands can be protonated at a lower pH and,instead of interacting electrostatically,can engage in hydrogen bonding.Importantly,by adjusting the proportion of TMA and MUA functional groups on the particles’surfaces,(χTMA:χMUA)NP,and/or particle sizes,the relative balance between electrostatic,hydrogen bonding,and van der Waals forces can be tuned,translating into pH-dependent stability versus aggregation of the MCNPs.In this way,MCNPs resist aggregation at the pH of healthy tissues and blood,but they precipitate or even crystallize at a narrow range of acidic pHs,characteristic of extracellular space surrounding tumors as well as intracellular endolysosomal compartments.We harnessed this propensity of MCNPs to aggregate at the desired pH to target low-pH lysosomes in cancer cells.As we showed,MCNPs with compositions around(χTMA:χMUA)NP=80:20 are noncytotoxic to normal

关 键 词：IMPAIRED walls AGGREGATION 

分 类 号：R73[医药卫生—肿瘤]