The enhancement of gene silencing efficiency with chitosan-coated liposome formulations of siRNAs targeting HIF-1α and VEGF

Şalva, Emine; Turan, Suna Özbaş; Eren, Fatih; Akbuğa, Jülide

doi:10.1016/j.ijpharm.2014.10.065

Cited by 45 publications

(20 citation statements)

References 37 publications

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“…Interestingly, our study found that HIF-1α level seems to be affected by VEGF as well as in tumor tissues ( Figure 5A and B). These results were consistent with those reported by Salva et al 30 They found that HIF-1α inhibition rate can reach 43% when VEGF gene was knocked down. HIF-1α expression is induced via activation of PI3K/AKT signaling, which is required for VEGF expression.…”

supporting

confidence: 93%

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

Chen

Sun

Shao

et al. 2017

IJN

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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.

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supporting

confidence: 93%

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

Chen

Sun

Shao

et al. 2017

IJN

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“…One way to go forward would be by using multiple gene targets. For example, combining VEGF targeting has shown to be synergistic with HIF‐1ɑ targeting, and another interesting approach would be to use plasmid encoding IL‐12 or IL‐12‐based cytokine combination therapies …”

Section: Discussionmentioning

confidence: 99%

Tumor gene therapy by systemic delivery of plasmid DNA with cell-penetrating peptides

et al. 2018

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Gene therapy is a prospective strategy for treating cancer. However, finding efficient and tumor‐specific gene delivery vectors remains an issue. Tumor responsive cell‐penetrating peptide (CPP) PepFect144 (PF144) has previously been shown to deliver reporter gene encoding plasmid DNA specifically into tumors upon systemic administration, but its capability to reduce tumor growth has not yet been evaluated. Here, we study the potential of PF144‐based anti‐angiogenic gene delivery to inhibit tumor growth by silencing vascular endothelial growth factor (VEGF) expression in tumors. This approach led to the inhibition of tumor growth in both the HT1080 fibrosarcoma model and orthotopic 4T1 breast tumor model. We additionally saw that the addition of αvβ3 integrin targeting did not further improve the tumor sensitive CPPs. Our results suggest that activatable cell‐penetrating peptide PF144 is a promising nonviral plasmid DNA delivery vector for cancer treatment.

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“…In another study, Salva et al [47] obtained enhanced silencing effect by using siRNAs targeting to VEGF and HIF-1α in different breast cancer cell lines such as MCF-7, MDA-MB-231, and MDA-MB-435. Two siRNAs were encapsulated into liposome coated with chitosan, and the co-delivery of siRNA VEGF and HIF-1α into liposomal form have significantly inhibited VEGF (89%) and the HIF-1α (62%) [47].…”

Section: Studies With Chitosan Formulations In Different Cancersmentioning

confidence: 99%

“…Chitosan has a great potential in siRNA-based cancer therapy studies, because it can be safely and efficiently delivered to cancer cells. It is reported that chitosan or modified chitosan nanoplexes and nanoparticles as delivery system exerted antitumoral effects in different cancers [43][44][45][46][47][48].…”

Section: Chitosanmentioning

confidence: 99%

Non-viral siRNA and shRNA Delivery Systems in Cancer Therapy

Şalva¹,

Ekentok²,

Turan³

et al. 2016

RNA Interference

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RNA interference represents a promising therapeutic strategy for the silencing of specific target genes in cancer therapy. Small interfering RNAs and DNA-based vectors encoding short hairpin RNAs provide sequence-specific post-transcriptional gene silencing by binding to its complementary RNA. For the therapeutic use of siRNA in cancer, efficient intracellular delivery is necessary. The efficient cancer therapy with RNAi is not still accomplished because of internalization and intracellular trafficking problems such as low transfection efficiency, enzyme degradation, inappropriate subcellular localization, and endosomal trapping of siRNAs in cells. Cancer is a complex disease including multiple genes and pathways. The most important benefits of siRNA therapy are high target specificity and non-toxicity compared with chemotherapy. The uptake of siRNA by cells without a carrier system is possible, but naked siRNA is mostly degraded with nucleases and activates the immune responses. Development of appropriate delivery systems is an important issue in the use of siRNA-based therapeutics. Non-viral delivery systems have great potential for safe and effective delivery of siRNA therapeutics to tumor cells. Nanocarriers such as nanoplexes, lipoplexes, nanoparticles, and liposomes have been commonly used for siRNA delivery. This chapter highlights the importance of non-viral delivery systems in vitro and in vivo cancer therapy.

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The enhancement of gene silencing efficiency with chitosan-coated liposome formulations of siRNAs targeting HIF-1α and VEGF

Cited by 45 publications

References 37 publications

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

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

Tumor gene therapy by systemic delivery of plasmid DNA with cell-penetrating peptides

Non-viral siRNA and shRNA Delivery Systems in Cancer Therapy

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