Multifunctional core/shell nanoparticles cross-linked polyetherimide-folic acid as efficient Notch-1 siRNA carrier for targeted killing of breast cancer.
In gene therapy, how genetic therapeutics can be efficiently and safely delivered into target tissues/cells remains a major obstacle to overcome. To address this issue, nanoparticles consisting of non-covalently coupled polyethyleneimine (PEI) and folic acid (FA) to the magnetic and fluorescent core/shell of Fe3O4@SiO2(FITC) was tested for their ability to deliver Notch-1 shRNA. Our results showed that Fe3O4@SiO2(FITC)/PEI-FA/Notch-1 shRNA nanoparticles are 64 nm in diameter with well dispersed and superparamagnetic. These nanoparticles with on significant cytotoxicity are capable of delivering Notch-1 shRNA into human breast cancer MDA-MB-231 cells with high efficiency while effectively protected shRNA from degradation by exogenous DNaseI and nucleases. Magnetic resonance (MR) imaging and fluorescence microscopy showed significant preferential uptake of Fe3O4@SiO2(FITC)/PEI-FA/Notch-1 shRNA nanocomplex by MDA-MB-231 cells. Transfected MDA-MB-231 cells exhibited significantly decreased expression of Notch-1, inhibited cell proliferation, and increased cell apoptosis, leading to the killing of MDA-MB-231 cells. In light of the magnetic targeting capabilities of Fe3O4@SiO2(FITC)/PEI-FA, our results show that by complexing with a second molecular targeting therapeutic, such as Notch-1 shRNA in this report, Fe3O4@SiO2(FITC)/PEI-FA can be exploited as a novel, non-viral, and concurrent targeting delivery system for targeted gene therapy as well as for MR imaging in cancer diagnosis.
Department of Biophysics, School of Life Science and Technology, University of Electronic Science and Technology of China, Chengdu 610054, Sichuan, P.R. China.
Hong
H
Yang
Department of Biophysics, School of Life Science and Technology, University of Electronic Science and Technology of China, Chengdu 610054, Sichuan, P.R. China.
Ying
Y
Li
Department of Biophysics, School of Life Science and Technology, University of Electronic Science and Technology of China, Chengdu 610054, Sichuan, P.R. China.
Tingting
T
Li
Department of Biophysics, School of Life Science and Technology, University of Electronic Science and Technology of China, Chengdu 610054, Sichuan, P.R. China.
Min
M
Xu
Department of Biophysics, School of Life Science and Technology, University of Electronic Science and Technology of China, Chengdu 610054, Sichuan, P.R. China.
Yin
Y
Chen
Department of Biophysics, School of Life Science and Technology, University of Electronic Science and Technology of China, Chengdu 610054, Sichuan, P.R. China.
Chunhui
C
Wu
Division of Trauma, Surgical Critical Care and Burns, University of California San Diego, CA 92103, USA.
Xitong
X
Dang
Department of Biophysics, School of Life Science and Technology, University of Electronic Science and Technology of China, Chengdu 610054, Sichuan, P.R. China.
Yiyao
Y
Liu
D017209:Apoptosis / Q000235:genetics; D001943:Breast Neoplasms / Q000000981:diagnostic imaging / Q000235:genetics* / Q000628:therapy; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000235:genetics; D005260:Female; D005492:Folic Acid / Q000737:chemistry; D018014:Gene Transfer Techniques; D015316:Genetic Therapy; D006801:Humans; D008279:Magnetic Resonance Imaging; D057145:Nanoshells / Q000008:administration & dosage / Q000737:chemistry*; D011108:Polymers / Q000737:chemistry; D034741:RNA, Small Interfering / Q000235:genetics / Q000627:therapeutic use; D011859:Radiography; D051881:Receptor, Notch1 / Q000235:genetics* / Q000627:therapeutic use; D012822:Silicon Dioxide / Q000737:chemistry
C497761:NOTCH1 protein, human; D011108:Polymers; D034741:RNA, Small Interfering; D051881:Receptor, Notch1; C433673:polyetherimide; D012822:Silicon Dioxide; D005492:Folic Acid