Cyclodextrin and Polyethylenimine Functionalized Mesoporous Silica Nanoparticles for Delivery of siRNA Cancer Therapeutics

Effective delivery holds the key to successful in vivo application of therapeutic small interfering RNA (siRNA). In this work, we have developed a universal siRNA carrier consisting of a mesoporous silica nanoparticle (MSNP) functionalized with cyclodextrin-grafted polyethylenimine (CP). CP provides...

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Detalles Bibliográficos
Autores principales: Shen, Jianliang, Kim, Han-Cheon, Su, Hua, Wang, Feng, Wolfram, Joy, Kirui, Dickson, Mai, Junhua, Mu, Chaofeng, Ji, Liang-Nian, Mao, Zong-Wan, Shen, Haifa
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Ivyspring International Publisher 2014
Materias:
Research Paper
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3966054/
https://www.ncbi.nlm.nih.gov/pubmed/24672582
http://dx.doi.org/10.7150/thno.8263
Descripción
Sumario:Effective delivery holds the key to successful in vivo application of therapeutic small interfering RNA (siRNA). In this work, we have developed a universal siRNA carrier consisting of a mesoporous silica nanoparticle (MSNP) functionalized with cyclodextrin-grafted polyethylenimine (CP). CP provides positive charge for loading of siRNA through electrostatic interaction and enables effective endosomal escape of siRNA. Using intravital microscopy we were able to monitor tumor enrichment of CP-MSNP/siRNA particles in live mice bearing orthotopic MDA-MB-231 xenograft tumors. CP-MSNP delivery of siRNA targeting the M2 isoform of the glycolytic enzyme pyruvate kinase (PKM2) resulted in effective knockdown of gene expression in vitro and in vivo. Suppression of PKM2 led to inhibition of tumor cell growth, invasion, and migration.

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