title: Cyclodextrin and polyethylenimine functionalized mesoporous silica nanoparticles for delivery of siRNA cancer therapeutics.
abstract: 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.
authors.affiliation: 1. MOE Key Laboratory of Bioinorganic and Synthetic Chemistry, School of Chemistry and Chemical Engineering, Sun Yat-sen University, Guangzhou, 510275, China, ; 2. Department of Nanomedicine, Houston Methodist Research Institute, Houston, Texas 77030, United States.
authors.forename: Jianliang
authors.initials: J
authors.lastname: Shen
authors.affiliation: 2. Department of Nanomedicine, Houston Methodist Research Institute, Houston, Texas 77030, United States.
authors.forename: Han-Cheon
authors.initials: HC
authors.lastname: Kim
authors.affiliation: 1. MOE Key Laboratory of Bioinorganic and Synthetic Chemistry, School of Chemistry and Chemical Engineering, Sun Yat-sen University, Guangzhou, 510275, China.
authors.forename: Hua
authors.initials: H
authors.lastname: Su
authors.affiliation: 2. Department of Nanomedicine, Houston Methodist Research Institute, Houston, Texas 77030, United States, ; 3. Department of Gastroenterology, The Tenth People's Hospital of Shanghai, Tongji University, Shanghai, 20072, China.
authors.forename: Feng
authors.initials: F
authors.lastname: Wang
authors.affiliation: 2. Department of Nanomedicine, Houston Methodist Research Institute, Houston, Texas 77030, United States, ; 4. CAS Key Laboratory for Biomedical Effects of Nanomaterials & Nanosafety, National Center for Nanoscience & Technology of China, Beijing 100190, China.
authors.forename: Joy
authors.initials: J
authors.lastname: Wolfram
authors.affiliation: 2. Department of Nanomedicine, Houston Methodist Research Institute, Houston, Texas 77030, United States.
authors.forename: Dickson
authors.initials: D
authors.lastname: Kirui
authors.affiliation: 2. Department of Nanomedicine, Houston Methodist Research Institute, Houston, Texas 77030, United States.
authors.forename: Junhua
authors.initials: J
authors.lastname: Mai
authors.affiliation: 2. Department of Nanomedicine, Houston Methodist Research Institute, Houston, Texas 77030, United States.
authors.forename: Chaofeng
authors.initials: C
authors.lastname: Mu
authors.affiliation: 1. MOE Key Laboratory of Bioinorganic and Synthetic Chemistry, School of Chemistry and Chemical Engineering, Sun Yat-sen University, Guangzhou, 510275, China.
authors.forename: Liang-Nian
authors.initials: LN
authors.lastname: Ji
authors.affiliation: 1. MOE Key Laboratory of Bioinorganic and Synthetic Chemistry, School of Chemistry and Chemical Engineering, Sun Yat-sen University, Guangzhou, 510275, China.
authors.forename: Zong-Wan
authors.initials: ZW
authors.lastname: Mao
authors.affiliation: 2. Department of Nanomedicine, Houston Methodist Research Institute, Houston, Texas 77030, United States, ; 5. Department of Cell and Developmental Biology, Weill Cornell Medical College, New York, NY10065, United States.
authors.forename: Haifa
authors.initials: H
authors.lastname: Shen
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use*; D001688:Biological Products / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use*; D003505:Cyclodextrins / Q000008:administration & dosage; D004195:Disease Models, Animal; D004337:Drug Carriers / Q000008:administration & dosage*; D005260:Female; D055785:Gene Knockdown Techniques; D051379:Mice; D053758:Nanoparticles / Q000008:administration & dosage*; D009369:Neoplasms / Q000628:therapy*; D011094:Polyethyleneimine / Q000008:administration & dosage; D011770:Pyruvate Kinase / Q000037:antagonists & inhibitors; D034741:RNA, Small Interfering / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use*; D012822:Silicon Dioxide / Q000008:administration & dosage
chemical_list: D000970:Antineoplastic Agents; D001688:Biological Products; D003505:Cyclodextrins; D004337:Drug Carriers; D034741:RNA, Small Interfering; D012822:Silicon Dioxide; D011094:Polyethyleneimine; D011770:Pyruvate Kinase
keywords: cancer therapy; delivery; gene silencing; mesoporous silica nanoparticle; siRNA