Comparative Study On EPR Effect Of Pure And Composite Nanomicelle In The Renal Tumor Zone

Objective: Cyclic perfusion of human renal tumor specimen was carried out by using pure nanomicelle labeled with propionate ammonium iodide and composite nanomicelle(PH response micelle).The dynamic evolution of iodine enrichment in human renal tumor was compared between pure and composite nanomicelle.It was confirmed that the enrichment of composite nanomicelle with the same size in renal tumor was higher than the pure nanomicelle.It is further proved that EPR effect also exist in the human tumor.Methods: 1.Three kinds of macromolecular nanomicelles with different sizes(45nm,70 nm,130nm)were selected,and the nanomicelles with different sizes were divided into three groups: A,B,and C.In each group,there were pure micelle and composite micelle.A1:45nm pure micelle,A2:45nm composite micelle,B1:70nm pure micelle,B2:70nm composite micelle,C1:130nm pure micelle,C2:130nm composite micelle.2.Three renal tumor samples were randomly perfused with each micelle;3.The GSI mode of GE Discovery HD750 CT at 1h?2h?3h?4h?5h and 6.0h after perfusion.CT values of renal tumor sites were measured and recorded respectively;4.We monitor the PH of the perfusion solution continuously and the urine output of the kidney,etc.After perfusion,the renal tumor specimens were fixed in 10% formalin and sent to the pathology department together with other specimens;5.The enrichment of each nano-micelle at the human kidney tumor site was measured through the GE ADW4.5 workstation,and a chart was drawn.SPSS19.0 statistical software was used to analyze the data results.Results:1.We were successed in setting up kidney specimen of extracorporeal circulation perfusion in vitro model.CT iodine base figure micelle allocation clear imaging.Each kidney produce urine volume 40.05±5.22 ml.PH of the Perfusion liquid maintained between 7.35-7.45.After the ending,the normal kidney tissue structure and cell apoptosis ratio had no obvious change(P > 0.05),and did not affect the postoperative pathological diagnosis;2.We found that the composite micelle in the tumor area iodine concentration was higher than that of pure micellar within the same group.But we compared the same type(pure micelle or composite micelle)nanomicelle in the groups,iodine,iodine in tumor area base curve and peak time,which was not identical.The concentration of 45 nm pure micelle in the tumor area was higher than that of 70 nm and 130 nm pure micelle.It suggestted that the EPR effect of distrinct size nanomicelle was different in the tumor area.EPR effect of the three groups of pure micelles was compared in the tumor area: 45 nm > 130 nm > 70 nm.Conclusions: 1.Compared with the pure micelle,the iodine enrichment in the tumor area of the composite micelle after perfusion was higher than that of the pure micelle.It indicated that the same size composite micelle had higher enrichment in the renal tumor area.It was further demonstrated that the existence of EPR in the tumor area.2.Different particle sizes and types of nano-micelles can lead to different enrichent and dynamic change processes in different tumor,which indicates that the EPR effect of different types and sizes of nanomicelles is different in the tumour area.The EPR effect of 45 nm pure micelle is higher than that of the 70 and 130 nm pure micelle in the tumour area.We can provide theoretical support for the clinical transformation of drug delivery system of macromolecule by investigating the EPR effect of different types and sizes of macromolecule in the tumour area.