Targeting CD133+ laryngeal carcinoma cells with chemotherapeutic drugs and siRNA against ABCG2 mediated by thermo/pH-sensitive mesoporous silica nanoparticles
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Mesoporous silica nanoparticles (MSNs) represent a new form of drug nanocarrier with thermo/pH-coupling sensitivity and site-specificity. CD133+ Hep-2 laryngeal cancer cells are responsible for multidrug resistance due to elevated expression of ABCG2. Since positively charged nanoparticles could easily uptake nucleic acids, we examined the possibility of using this new drug delivery system to simultaneously deliver different chemotherapeutic drugs and siRNA targeting ABCG2. Our results demonstrated that both antitumor drugs and siRNA against ABCG2 were successfully delivered into CD133+ cancer cells by loaded MSNs. Down-regulation of ABCG2 significantly enhanced the efficacy of chemotherapeutic drug-induced apoptosis in laryngeal carcinoma cells. Furthermore, the chemotherapeutic drug and siRNA loaded nanoparticles inhibited tumor growth in vivo in a laryngeal cancer mouse model.
KeywordsCD133+ Laryngeal carcinoma ABCG2 siRNA nanoparticle
Mesoporous silica nanoparticles in this study were kindly provided by the State Key Laboratory of Inorganic Synthesis and Preparative Chemistry, College of Chemistry, Jilin University. This work is supported by the National Natural Science Foundation of China (No. 81572653) and Jilin Province Natural Science Foundation of China, No. 20130101151JC, and the Chinese Ministry of Education Projects of Doctoral New teachers, No. 20120061120092.
Conflicts of interest
All applicable national guidelines for the care and use of animals were followed.
- 8.Meyer zu Schwabedissen HE, Kroemer HK. In vitro and in vivo evidence for the importance of breast cancer resistance protein transporters (BCRP/MXR/ABCP/ABCG2). Handb Exp Pharmacol. 2011;(201):325–71.Google Scholar
- 9.Yang JP, Liu Y, Zhong W, Yu D, Wen LJ, Jin CS. Chemoresistance of CD133+ cancer stem cells in laryngeal carcinoma. Chin Med J (Engl). 2011;124(7):1055–60.Google Scholar
- 10.Wu CP, Xie M, Zhou L, Tao L, Zhang M, Tian J. Cooperation of side population cells with CD133 to enrich cancer stem cells in a laryngeal cancer cell line. Head Neck. 2014;36(9):1279–87.Google Scholar
- 11.Mannelli G, Magnelli L, Deganello A, Busoni M, Meccariello G, Parrinello G, et al. Detection of putative stem cell markers, CD44/CD133, in primary and lymph node metastases in head and neck squamous cell carcinomas. A preliminary immunohistochemical and in vitro study. Clin Otolaryngol. 2015;40(4):312–20.CrossRefPubMedGoogle Scholar
- 20.Maignan M, Koch FX, Kraemer M, Lehodey B, Viglino D, Monnet MF, et al. Impact of laryngeal tube use on chest compression fraction during out-of-hospital cardiac arrest. A prospective alternate month study. Resuscitation. 2015.Google Scholar