In vivo bacteriophage peptide display to tailor pharmacokinetics of biological nanoparticles.
In vivo bacteriophage peptide display to tailor pharmacokinetics of biological nanoparticles.
复制标题
体内噬菌体肽展示可定制生物纳米颗粒的药代动力学。
DOI：
10.1007/s11307-014-0762-z
复制
发表时间：
2014
影响因子：
3.1
通讯作者：
Deutscher,SusanL
中科院分区：
文献类型：
--
作者：
Newton-Northup,JessicaR;Dickerson,MarieT;Kumar,SenthilR;Smith,GeorgeP;Quinn,ThomasP;Deutscher,SusanL
PurposeClinical use of most radiolabeled targeting agents has been limited because of the uptake and retention in kidney and/or liver. We hypothesized that bacteriophage (phage) display could be exploited to select for peptide sequences with fast clearance and low kidney uptake with the added ability to redirect phage clearance away from the reticuloendothelial system towards the kidney possessing rapid kidney clearance.ProceduresIn vivophage display was performed to identify peptides displayed on phage that were excreted rapidly into the urine of mice. A novelin vitroassay using kidney cells, developed to predictin vivokidney retention, andin vivopharmacokinetic analyses were performed to characterize selected peptides/phage clones.ResultsForty-three renal clearance clones (RCC) were identified.In vivomixing experiments andin vitrokidney cell assays identified RCC1-02 as the lead compound.In vivoanalysis of fluorescently labeled phage clones demonstrated the ability of RCC1-02 peptide to redirect the biodistribution of the large phage particle towards excretion via the kidney. Pharmacokinetic analysis of [111In]-radiolabeled peptides revealed that kidney retention of the control ErBB-2-avid peptide, [111In]DOTA-KCCYSL, at 2-h postinjection was 5.7 ± 0.7 %ID/g. In comparison, [111In]DOTA-RCC1-02 had kidney retention values of 1.66 ± 0.43 %ID/g, respectively.ConclusionsIn vivophage display can identify phage and corresponding peptides that rapidly clear the renal system. In the future, these peptides may be used to impart favorable pharmacokinetics onto a wide range of radioimaging or therapeutic macromolecules.
