Controlling Assembly Of Paired Gold Clusters Within Apoferritin And Its Biomedical Imagins

Functional nanostructures with high biocompatibility and stability, low toxicity and specificity of targeting to desired organs or cells are of great interest in nanobiology and medicine. However, the challenge is to integrate all these desired features into a single nanobiostructure, which can be applied to biomedical applications and eventually in clinical settings. In this context, we designed a strategy to assemble two gold nanoclusters at the ferroxidase active sites of ferritin heavy chain. Our studies showed that the resulting nanostructures (Au-Ft) retain not only the intrinsic fluorescence properties of noble metal, but gain enhanced intensity, show a red-shift and exhibit tunable emissions due to the coupling interaction between the paired Au clusters. Furthermore, Au-Ft possessed the well defined nanostructure of native ferritin, showed organ-specific targeting ability, high biocompatibility and low cytotoxicity. The current study demonstrates that an integrated multimodal assembly strategy is able to generate stable and effective biomolecule-noble metal complexes of controllable size and with desirable fluorescence emission characteristics. Such agents are ideal for targeted in vitro and in vivo imaging. These results thus open new opportunities for biomolecule-guided nanostructure assembly with great potential for biomedical applicationsIn this paper, for making the idea of assembling the Au clusters into apoferritin to be true, the strategy which is used is "point controlling". Apoferritin is suitable to the condition which this idea needs:firstly, having the point which the reaction needs-the histidine at the ferroxidase active sites of apoferritin can bind Au3+ secondly, having the reactor which the reaction needs-the interior cavity of apoferritin is 10 nm, and the big pore of it is about 1 nm; thirdly, the chemical and physical characteristics of apoferritin are very stable, and the apoferritin can endure strong acid and alkali. By controlling the speed of the OH" reducing Au3+, we can get the size of the Au clusters we need. Through cryo-EM, HAADF-STEM, HRTEM and so on we can prove that we have assembled paired far-red Au clusters in apoferritin..Using the characteristic of far-red fluorescence of paired far-red Au clusters, we have done the research in the biomedical imaging:(1) Paired far-red Au clusters used in the cell fluorescent imaging. We choose two kinds of cell, one is Caco-2 which has the receptor of apoferritin and the other is HepG2 which has no receptor of apoferritin. Paired far-red Au clusters within apoferritin can absorb on the surface of cell membrane of Caco-2, but can not absorb on the surface of cell membrane of HepG2.(2) Paired far-red Au clusters used in the animal targeting fluorescent imaging. We can see the fluorescent imaging of the shape of two kidneys at the back of mice after several hours by vein injecting. It clearly says that paired far-red Au clusters reached the position of kidneys.Through this paper it can confirm that far-red Au clusters within apoferritin can have a good prospect in the future.