Charge reversible calcium phosphate lipid hybrid nanoparticle for siRNA delivery
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Rong-Qiao Cai1, Dao-Zhou Liu1,*, Han Cui1, Ying Cheng1, Miao Liu1, Bang-Le Zhang1, Qi-Bing Mei2 and Si-Yuan Zhou1,2
1Department of Pharmaceutics, School of Pharmacy, Fourth Military Medical University, Xi’an, 710032, China
2Key Laboratory of Gastrointestinal Pharmacology of Chinese Materia Medica of the State Administration of Traditional Chinese Medicine, Fourth Military Medical University, Xi’an, 710032, China
*Author contributed equally to this work
Si-Yuan Zhou, email: firstname.lastname@example.org
Keywords: lipid hybrid nanoparticles, charge conversional, calcium phosphate, siBcl-2
Received: October 31, 2016 Accepted: April 15, 2017 Published: April 27, 2017
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.
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