Construction of 131I-labeled and dual-drug loaded multifunctional nanoparticles

Abstract

Objective To construct 131I-labeled and dual-drug-loaded multifunctional mesoporous silica(mSiO2) nanoparticles, and to investigate its characteristics, drug release kinetics, and uptake by anaplastic thyroid cancer(ATC) cells. Methods The mSiO2 nanoparticles were constructed through the conventional template method. 17-allylamino-17-demethoxygeldanamycin(17-AAG) and Torin2 were loaded at equal concentrations, and bovine serum albumin was connected to the amino-modified nanoparticles. The characteristics, encapsulation efficiency, and drug loading rates of the nanoparticles were then investigated. Drug release was analyzed by high-performance liquid chromatography. The nanoparticles were labeled with 131I using the chloramine-T method. The time-dependent cellular uptake of 131I-labeled nanoparticles was also analyzed to evaluate the uptake and retention of the nanoparticles in ATC cells. T'-test was used for data analysis using SPSS19.0 software. Results The mSiO2 nanoparticles and (17-AAG+Torin2) @mSiO2-BSA-131I samples were successfully constructed. The average diameters were 170 nm to 250 nm and 200 nm to 300 nm, respectively, with good dispersibility and spherical shape. The labeling rate and radiochemical purity of the 131I-nanoparticles were 66.31% to 78.25% and 98.80% to 99.42%, respectively. The drug loading rates of 17-AAG and Torin2 were 7.31%±0.22% and 6.04%±0.79%, and their encapsulation efficiencies were 86.21%±1.32% and 85.17%±2.05%, respectively. The nanoparticles loaded with 17-AAG and Torin2 exhibited slow drug release behavior. The uptake of (17-AAG+Torin2) @mSiO2-BSA-131I was higher than that of Na131I(t=32.63-109.31, all P<0.01) and could reach its maximum level at 3 h after incubation. Conclusions The mSiO2 nanoparticles loaded with 17-AAG and Torin2 and labeled with 131I exhibited slow drug release behavior. ATC cells could uptake(17-AAG+ Torin2)@mSiO2-BSA-131I rapidly. Key words: Iodine radioisotopes; Silicon dioxide; Nanoparticles; Molecular targeted drugs; Anaplastic thyroid cancer