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Comparative Study
. 2018 Jan 23;51(3):1-10.
doi: 10.1590/1414-431X20176650.

Low density lipoprotein modified silica nanoparticles loaded with docetaxel and thalidomide for effective chemotherapy of liver cancer

Man Ao, Xu Xiao, Yazhou Ao
Comparative Study

Low density lipoprotein modified silica nanoparticles loaded with docetaxel and thalidomide for effective chemotherapy of liver cancer

Man Ao et al. Braz J Med Biol Res. .

Abstract

In the present study, we successfully developed a docetaxel (DTX) and thalidomide (TDD) co-delivery system based on low density lipoprotein (LDL) modified silica nanoparticles (LDL/SLN/DTX/TDD). By employing the tumor homing property of LDL and the drug-loading capability of silica nanoparticles, the prepared LDL/SLN/DTX/TDD was expected to locate and specifically deliver the loaded drugs (DTX and TDD) to achieve effective chemotherapy of liver cancer. In vitro analysis revealed that nano-sized LDL/SLN/DTX/TDD with decent drug loading capabilities was able to increase the delivery efficiency by targeting the low density lipoprotein receptors, which were overexpressed on HepG2 human hepatocellular liver carcinoma cell line, which exerted better cytotoxicity than unmodified silica nanoparticles and free drugs. In vivo imaging and anti-cancer assays also confirmed the preferable tumor-homing and synergetic anti-cancer effects of LDL/SLN/DTX/TDD.

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Figures

Figure 1.
Figure 1.. Particle size distribution (A) of amine-decorated silica nanoparticles (SLNs) and low density lipoprotein (LDL)/SLNs. Mean particle size, zeta potential and poly dispersion index (PDI) measurements (B) of amine-decorated SLNs and LDL/SLNs. Data are reported as means±SD (n=3).
Figure 2.
Figure 2.. In vitro docetaxel (DTX) and thalidomide (TDD) of the drug release system LDL/SLN/DTX/TDD at different pH values (7.4 and 5.0). Data are reported as means±SD (n=3). LDL: low density lipoprotein; SLN: silica nanoparticles. **P<0.01 vs pH 7.4 (two-tailed Student's t-test).
Figure 3.
Figure 3.. In vitro quantitative flow cytometric analysis of free coumarin 6 (C6), C6-loaded SLN/DTX/TDD and C6-loaded LDL/SLN/DTX/TDD with and without low density lipoprotein (LDL) pretreatment in HepG2 cells for 2, 4, and 6 h of incubation. Data are reported as means±SD (n=3). SLN: silica nanoparticles; DTX: docetaxel; TDD: thalidomide; HA: hyaluronic acid. **P<0.01 vs LDL pretreated groups (two-tailed Student's t-test).
Figure 4.
Figure 4.. A, Cytotoxicity of free LDL/SLNs after 48 h incubation with HepG2 cells. B, Cytotoxicity of free DTX, free TDD, LDL/SLN/DTX, LDL/SLN/TDD and LDL/SLN/DTX/TDD against HepG2 cells after 48 h incubation. LDL: low density lipoprotein; SLN: silica nanoparticles; DTX: docetaxel; TDD: thalidomide. Data are reported as means±SD (n=3). **P<0.01 vs LDL/SLN/DTX or LDL/SLN/TDD (two-tailed Student's t-test).
Figure 5.
Figure 5.. A, In vivo time-dependent tumor-targeting images after intravenous B injection of DiR-loaded nanoparticles in HepG2 tumor-bearing mice. B, Representative ex vivo mean fluorescence intensity of dissected tumors and major organs at 6 h post-injection. LDL: low density lipoprotein; SLN: silica nanoparticles; DTX: docetaxel; TDD: thalidomide. Data are reported as means±SD (n=3). **P<0.01 vs SLN/DTX/TDD (two-tailed Student's t-test).
Figure 6.
Figure 6.. Tumor volume (A) and body weight (B) of the different groups. C, HE staining of tumor tissue of HepG2 tumor-bearing BALB/c nude mice after intravenous injection of different formulations. The measurement of tumor volumes and the injection of formulations were repeated every 2 days for 2 weeks. Dose: 10 mg/kg DTX and/or 25 mg/kg TDD per mouse. LDL: low density lipoprotein; SLN: silica nanoparticles; DTX: docetaxel; TDD: thalidomide. Data are reported as means±SD (n=53). **P<0.01 vs saline (panel A); **P<0.01 vs Free DTX (panel B) (two-tailed Student's t-test).
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