Multi-component driven fluorescence composite nanospheres coating strategy: Spectral properties, release, tumor imaging and bioactivity evaluation in a simulated gastrointestinal microenvironment

Abstract

Carborane has been widely studied for its excellent tumor-targeting and other properties, but its poor water solubility and inability to visualize the treatment limit the application of carborane. Therefore, in this paper, two different indol-nido-carbrane potassium salt-crown ether-sodium alginate polymers were obtained by designing an indole dye with good fluorescence performance, combining it with nido-carbrane potassium salt, and then loading it into sodium alginate and different crown ethers. Among them, the polymer (INC-2) formed by loading dipropenone-18-crown-6 and sodium alginate is considered to be the most promising anti-tumor drug with good fluorescence properties. The optical properties test showed that INC-2 had good fluorescence properties. The results of atomic force microscopy (AFM) and transmission electron microscopy (TEM) manifested that INC-2 was a smooth and uniform sphere, which was conducive to absorption in vivo. Through the cell proliferation toxicity test (CCK8), it was found that when the concentration was 300 μg/mL, the highest inhibition rates of INC-2 on HCT-116, HeLa and L02 were 53.43 %, 61.19 % and 17.06 %, respectively, demonstrating that the polymer had significant anti-tumor activity and low cytotoxicity. In addition, INC-2 was applied to cell imaging, which could enter and be well absorbed by HCT-116 and HeLa cells. Further in vivo imaging experiments showed that INC-2 could be well targeted to the gastrointestinal tract of mice. In summary, this design not only solves the problem of poor water solubility of carborane, improves its bioavailability, but also provides excellent visual fluorescence targeting effect.