Recent progress in development of siRNA delivery vehicles for cancer therapy

Kim, Hyun Jin; Kim, Ah-Ram; Miyata, Kanjiro; Kataoka, Kazunori

doi:10.1016/j.addr.2016.06.011

Cited by 362 publications

(308 citation statements)

References 195 publications

Supporting

Mentioning

305

Contrasting

Order By: Relevance

“…The siRNA is a double-stranded RNA with typically 21–23 nucleotides having 3′ two-nucleotide overhangs [6]. Its negative charge allows the use of the cationic carriers including lipids, dendrimers, natural polymers and PEI [15]. Recently, lipopolymetric NP, PEI-functionalized gold nanorods and PEI NP have been reported in the NP/siRNA-based therapy strategies for GBM [16,17,18,19].…”

Section: Discussionmentioning

confidence: 99%

PEI-Coated Fe3O4 Nanoparticles Enable Efficient Delivery of Therapeutic siRNA Targeting REST into Glioblastoma Cells

Wang

Degirmenci

Xin

et al. 2018

IJMS

View full text Add to dashboard Cite

Glioblastomas (GBM) are the most frequent brain tumors lacking efficient treatment. The increasingly elucidated gene targets make siRNA-based gene therapy a promising anticancer approach, while an efficient delivery system is urgently needed. Here, polyethyleneimine (PEI)-coated Fe3O4 nanoparticles (NPs) have been developed and applied for siRNA delivery into GBM cells to silence repressor element 1-silencing transcription factor (REST). The prepared PEI-coated Fe3O4 NPs were characterized as magnetic nanoparticles with a positive charge, by transmission electronic microscopy, dynamic light-scattering analysis and a magnetometer. By gel retardation assay, the nanoparticles were found to form complexes with siRNA and the interaction proportion of NP to siRNA was 2.8:1. The cellular uptake of NP/siRNA complexes was verified by prussian blue staining, fluorescence labeling and flow cytometry in U-87 and U-251 GBM cells. Furthermore, the REST silencing examined by realtime polymerase chain reaction (PCR) and Western blotting presented significant reduction of REST in transcription and translation levels. Upon the treatment of NP/siRNA targeting REST, the GBM cell viabilities were inhibited and the migration capacities were repressed remarkably, analyzed by cell counting kit-8 and transwell assay separately. In this study, we demonstrated the PEI-coated Fe3O4 nanoparticle as a vehicle for therapeutic siRNA delivery, at an appropriate NP/siRNA weight ratio for REST silencing in GBM cells, inhibiting cell proliferation and migration efficiently. These might represent a novel potential treatment strategy for GBM.

show abstract

Section: Discussionmentioning

confidence: 99%

PEI-Coated Fe3O4 Nanoparticles Enable Efficient Delivery of Therapeutic siRNA Targeting REST into Glioblastoma Cells

Wang

Degirmenci

Xin

et al. 2018

IJMS

View full text Add to dashboard Cite

show abstract

“…1,2 Over the last few years, great efforts have been focused on developing stable RNAi-based drugs using different chemical modifications in their structure, increasing their lifetime under plasma conditions and reducing their offtarget effects. [3][4][5] However, the use of naked nucleic acids is still limited because they are rapidly eliminated by the kidneys 6 and, if siRNA reaches the target cells, it lacks the mechanism to enter the cytoplasm. Different biomaterials have been used to protect RNAibased drugs, increasing the RNAi functionality, such as lipidbased delivery systems, polymeric-based delivery systems, conjugated-based delivery systems, and cell-penetrating peptides.…”

Section: Introductionmentioning

confidence: 99%

Stable and efficient generation of poly(β-amino ester)s for RNAi delivery

Dosta

Ramos

Borrós

2018

Mol. Syst. Des. Eng.

View full text Add to dashboard Cite

abCationic polymers are promising delivery systems for RNAi due to their ease of manipulation, scale-up conditions and transfection efficiency. However, some properties, such as stability and targeting, remain challenging to overcome. In this report, different modifications in poly(β-amino ester) (pBAE) structures have been explored to overcome these limitations. Recent studies have demonstrated that hydrophobicity plays a key role in controlling electrostatic interactions of plasma proteins with nanoparticles. Results show that a slight increase in the polymer hydrophobicity increases its siRNA packaging capacity, stability, and transfection efficiency. Consequently, polyplexes prepared with these hydrophobic structures are functional after incubation times longer than 48 hours in serum-containing medium. In addition, newly designed polymers were end-modified using different oligopeptide moieties in order to confer cell-specificity, as previously reported. Therefore, it can be concluded that these newly optimized pBAE polymers present great potential as delivery vectors to specifically drive therapeutic RNA-based nucleic acids in a cell-specific manner under physiological conditions.

show abstract

“…Widely used for the delivery of siRNA are cationic lipids or cationic Recently, various strategies have been utilized to design more complex structure with components of surface, intermediate layer, and core. 22 These components drive electrostatic interaction with siRNA and increase siRNA loading in vectors. 23 We have developed a core-membrane siRNA delivery system called PLCP composed of CaP nanoparticles core coated with PCL.…”

Section: Discussionmentioning

confidence: 99%

VEGF siRNA delivered by polycation liposome-encapsulated calcium phosphate nanoparticles for tumor angiogenesis inhibition in breast cancer

Chen

Sun

Shao

et al. 2017

IJN

View full text Add to dashboard Cite

Angiogenesis plays an important role in tumor development and metastasis, and many cancer cells upregulate VEGF expression to promote angiogenesis. Silencing VEGF expression by RNA interference is expected to be a promising strategy to suppress the tumor growth. However, low transfection efficiency and instability are the main barriers for small interfering RNA (siRNA) delivery. In this study, we developed polycation liposome-encapsulated calcium phosphate nanoparticles (PLCP) for siRNA delivery in vivo. VEGF expression silencing effect in MCF-7 cells was investigated by real-time quantitative polymerase chain reaction and Western blot assay. VEGF siRNA mediated by PLCP can reduce 60%–80% VEGF expression in vitro, which was significantly higher than that mediated by Lipofectamine 2000. Furthermore, significant tumor growth and angiogenesis inhibition were observed in MCF-7 xenografts mice when treated with PLCP/VEGF siRNA or combined with doxorubicin. In conclusion, the combination of silencing VEGF expression and chemotherapeutics would be a potential treatment for cancer therapy.

show abstract

Recent progress in development of siRNA delivery vehicles for cancer therapy

Cited by 362 publications

References 195 publications

PEI-Coated Fe3O4 Nanoparticles Enable Efficient Delivery of Therapeutic siRNA Targeting REST into Glioblastoma Cells

PEI-Coated Fe3O4 Nanoparticles Enable Efficient Delivery of Therapeutic siRNA Targeting REST into Glioblastoma Cells

Stable and efficient generation of poly(β-amino ester)s for RNAi delivery

VEGF siRNA delivered by polycation liposome-encapsulated calcium phosphate nanoparticles for tumor angiogenesis inhibition in breast cancer

Contact Info

Product

Resources

About