Abstract
Bcl-2 gene is an important target to treat lung cancer. The small interference RNA (siRNA) of Bcl-2 gene (siBcl-2) can specifically silence Bcl-2 gene. However, naked siBcl-2 is difficult to accumulate in the tumor tissue to exert its activity. In this paper, a calcium phosphate lipid hybrid nanoparticle that possessed charge reversible property was prepared to enhance the activity of siBcl-2 in vivo. The average diameter and zeta potential of siBcl-2 loaded calcium phosphate lipid hybrid nanoparticles (LNPS@siBcl-2) were 80 nm and −13 mV at pH7.4 whereas the diameter and zeta potential changed to 1506 nm and +9 mV at pH5.0. LNPS@siBcl-2 could efficiently deliver siBcl-2 to the cytoplasm and significantly decreased the expression of Bcl-2 in A549 cells. Moreover, the in vivo experimental results showed that most of the Cy5-siBcl-2 accumulated in tumor tissue after LNPS@Cy5-siBcl-2 was administered to tumor-bearing mice by tail vein injection. Meanwhile, the expression of Bcl-2 was decreased but the expression of the BAX and Caspase-3 was increased in tumor tissue. LNPS@siBcl-2 significantly inhibited the growth of tumor in tumor-bearing mice without any obvious systemic toxicity. Thus, the charge reversible calcium phosphate lipid hybrid nanoparticle was an excellent siBcl-2 delivery carrier to improve the activity of siBcl-2 in vivo. LNPS@siBcl-2 has potential in the treatment of lung cancer.
Highlights
In 2012, there were 1.82 million new lung cancer cases in the world. 1.56 million deaths were resulted from lung cancer, which took up 19.4% of death from cancer
LNPS@siBcl-2 was stable in 10 days in PBS
The siBcl-2 encapsulated in hybrid nanoparticles was stable when LNPS@siBcl-2 incubated with RNase A for 2 h (Figure 2D)
Summary
In 2012, there were 1.82 million new lung cancer cases in the world. 1.56 million deaths were resulted from lung cancer, which took up 19.4% of death from cancer. In 2012, there were 1.82 million new lung cancer cases in the world. 1.56 million deaths were resulted from lung cancer, which took up 19.4% of death from cancer. Lung cancer is the one with the highest morbidity and mortality rate in China. RNA interference (RNAi) therapy has arisen as a new technique for anticancer therapy owning to its specific gene silencing effect [4, 5]. To construct an effective delivery carrier for small interference RNA (siRNA) is the key step for RNAi therapy [6, 7]. The siRNA delivery carrier included virus-based vehicle, lipidbased nanoparticles, [8, 9] atelocollagen nanoparticles [10] and polyethyleneimine [11] etc. The in vivo transfection efficiency and safety of those carriers need to be further improved
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