Adsorption of proteins to nanoparticles(NPs),a complex process that results in a protein corona,is controlled by NP surface properties that define NP interactions in vivo.Efforts to control adsorbed protein quantity t...Adsorption of proteins to nanoparticles(NPs),a complex process that results in a protein corona,is controlled by NP surface properties that define NP interactions in vivo.Efforts to control adsorbed protein quantity through surface modification have led to improvements in circulation time or biodistribution.Still,current approaches have yet to be identified to control adsorbed protein identities within the corona.Here,we report the development and characterization of diverse zwitterionic peptides(ZIPs)for NP anti-fouling surface functionalization with specific and controllable affinity for protein adsorption profiles defined by ZIP sequence.Through serum exposure of ZIP-conjugated NPs and proteomics analysis of the resulting corona,we determined that protein adsorption profiles depend not on the exact composition of the ZIPs but on the sequence and order of charges along the sequence(charge motif).These findings pave the way for developing tunable ZIPs to orchestrate specific ZIP-NP protein adsorption profiles as a function of ZIP charge motif to better control cell and tissue specificity and pharmacokinetics and provide new tools for investigating relationships between protein corona and biological function.Furthermore,overall ZIP diversity enabled by the diversity of amino acids may ameliorate adaptive immune responses.展开更多
基金study was provided by the National Institute of Health(NIH)F31AR076874,R01DE018023,R01AR056696,and the National Science Foundation(NSF)CBET-1450897 and DMR-2103553.
文摘Adsorption of proteins to nanoparticles(NPs),a complex process that results in a protein corona,is controlled by NP surface properties that define NP interactions in vivo.Efforts to control adsorbed protein quantity through surface modification have led to improvements in circulation time or biodistribution.Still,current approaches have yet to be identified to control adsorbed protein identities within the corona.Here,we report the development and characterization of diverse zwitterionic peptides(ZIPs)for NP anti-fouling surface functionalization with specific and controllable affinity for protein adsorption profiles defined by ZIP sequence.Through serum exposure of ZIP-conjugated NPs and proteomics analysis of the resulting corona,we determined that protein adsorption profiles depend not on the exact composition of the ZIPs but on the sequence and order of charges along the sequence(charge motif).These findings pave the way for developing tunable ZIPs to orchestrate specific ZIP-NP protein adsorption profiles as a function of ZIP charge motif to better control cell and tissue specificity and pharmacokinetics and provide new tools for investigating relationships between protein corona and biological function.Furthermore,overall ZIP diversity enabled by the diversity of amino acids may ameliorate adaptive immune responses.
