Multi-step encapsulation of chemotherapy and gene silencing agents in functionalized mesoporous silica nanoparticles

Jianliang Shen, Haoran Liu, Chaofeng Mu, Joy Wolfram, Wei Zhang, Han Cheon Kim, Guixian Zhu, Zhongbo Hu, Liang Nian Ji, Xuewu Liu, Mauro Ferrari, Zong Wan Mao, Haifa Shen

Research output: Contribution to journalArticle

24 Scopus citations

Abstract

Drug to carrier ratio is an important consideration in designing drug platforms, since a low loading capacity necessitates the use of high doses of carriers, which can result in side effects. Here, we have engineered a platform to co-deliver small molecule drugs and small interfering RNA (siRNA). This platform consists of cyclodextrin-grafted polyethylenimine (CP) functionalized mesoporous silica nanoparticles (MSNP). A unique multi-step encapsulation procedure was used to obtain a high loading capacity for doxorubicin (DOX) and siRNA oligos specific for the PKM2 gene that encodes pyruvate kinase M2, an enzyme catalyzing the final rate-limiting step in glycolysis. We systematically characterized this platform (CP-MSNP@DOX/PKM2) in vitro and evaluated its therapeutic efficacy in vivo with a mouse model of triple negative breast cancer (TNBC). Exposure of TNBC cells to CP-MSNP@DOX/PKM2 resulted in suppressed target gene expression, reduced cell proliferation, and enhanced apoptosis. Intravenous administration of the drug substantially decreased the tumor burden in comparison to DOX or siRNA monotherapy. In conclusion, we have developed a platform for efficient co-delivery of small molecule drugs and therapeutic siRNA.

Original languageEnglish (US)
Pages (from-to)5329-5341
Number of pages13
JournalNanoscale
Volume9
Issue number16
DOIs
StatePublished - Apr 28 2017
Externally publishedYes

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ASJC Scopus subject areas

  • Materials Science(all)

Cite this

Shen, J., Liu, H., Mu, C., Wolfram, J., Zhang, W., Kim, H. C., Zhu, G., Hu, Z., Ji, L. N., Liu, X., Ferrari, M., Mao, Z. W., & Shen, H. (2017). Multi-step encapsulation of chemotherapy and gene silencing agents in functionalized mesoporous silica nanoparticles. Nanoscale, 9(16), 5329-5341. https://doi.org/10.1039/c7nr00377c