Furin controlled intracellular assembly of nanoparticles for enhanced uptake of radionuclide in living cells

【摘要】：Protease controlled assembly of nanostructures has remained challenging for supramolecular chemists.Herein,we report a condensation system which could be controlled by furin,an important protease which is associated with early development of cancer.We designed Acetyl-Arg-Val-Arg-Arg-Cys(StBu)-Tyr(I-125)-CBT(1) for self-assembling radioactive nanoparticles(I 125-NPs) in living cells.Its scrambled control Acetyl-Arg-Tyr(I-125)-Arg-Cys(StBu)-Arg-Val-CBT(1-scr) which can not be cleaved by furin was also prepared for study in parallel.Upon furin cleavage at 100 μM,the cold form of compound 1(i.e.,1-cold) can condense to form macrocyclized dimer which self-assembles to form I-NPs with a mean diameter of 150 nm.Cell uptake indicated that more of 1 than 1-scr was uptaken by breast cancer cell MDA-MB-231.Interestingly,cells incubated with 1,1-scr,or 1-scr with 100 μM 1-scr-cold showed similar efflux curves while that of cells incubated with 1 and 100 μM of 1-cold was different.At 160 min after cell efflux,17.9% of the radioactivity was retained in the cells incubated with 1 and 100 μM 1-cold while the percentages of other three groups are 4.4%,3.7%,and 3.7% respectively.By means of intracellular assembly of radioactive nanoparticles,this provides us with a new method of furin detection or cancer early detection.