Polyethylene glycol&amp;ndash;poly(&amp;epsilon;-benzyloxycarbonyl-L-lysine)-conjugated VEGF siRNA for antiangiogenic gene therapy in hepatocellular carcinoma

Wang, Gangmin; Gao, Xiaolong; Gu, GuoJun; Shao, Zhihong; Li, Minghua; Wang, Peijun; Yang, Jianrong; Cai, Xiaojun; Li, YongYong

doi:10.2147/ijn.s131078

Cited by 26 publications

(15 citation statements)

References 43 publications

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“…PEG-SS-PLL-siVEGF NP treated mice showed reduced tumor growth compared to controls. Furthermore, histopathology and Western blot analysis of excised tumors showed reduced VEGF expression [73].…”

Section: Pll-derived Nanosystemsmentioning

confidence: 96%

Lipid and Polymer-Based Nanoparticle siRNA Delivery Systems for Cancer Therapy

2020

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RNA interference (RNAi) uses small interfering RNAs (siRNAs) to mediate gene-silencing in cells and represents an emerging strategy for cancer therapy. Successful RNAi-mediated gene silencing requires overcoming multiple physiological barriers to achieve efficient delivery of siRNAs into cells in vivo, including into tumor and/or host cells in the tumor micro-environment (TME). Consequently, lipid and polymer-based nanoparticle siRNA delivery systems have been developed to surmount these physiological barriers. In this article, we review the strategies that have been developed to facilitate siRNA survival in the circulatory system, siRNA movement from the blood into tissues and the TME, targeted siRNA delivery to the tumor or specific cell types, cellular uptake, and escape from endosomal degradation. We also discuss the use of various types of lipid and polymer-based carriers for cancer therapy, including a section on anti-tumor nanovaccines enhanced by siRNAs. Finally, we review current and recent clinical trials using NPs loaded with siRNAs for cancer therapy. The siRNA cancer therapeutics field is rapidly evolving, and it is conceivable that precision cancer therapy could, in the relatively near future, benefit from the combined use of cancer therapies, for example immune checkpoint blockade together with gene-targeting siRNAs, personalized for enhancing and fine-tuning a patient’s therapeutic response.

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Section: Pll-derived Nanosystemsmentioning

confidence: 96%

Lipid and Polymer-Based Nanoparticle siRNA Delivery Systems for Cancer Therapy

2020

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“…1,2 Owing to the low percentage of HCC patients who are eligible for surgery and the high tumor recurrence rates, chemotherapy is still a major clinical method for HCC treatments. 3 Many traditional chemotherapy drugs have been utilized for the HCC therapy, but most of them have been ineffective.…”

Section: Introductionmentioning

confidence: 99%

siRNA-loaded selenium nanoparticle modified with hyaluronic acid for enhanced hepatocellular carcinoma therapy

Xia¹,

Guo²,

Xu³

et al. 2018

IJN

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Background Small interfering RNA (siRNA) as a new therapeutic modality holds promise for cancer treatment. However, the traditional viral carriers are prone to immunogenicity and risk of insertional mutagenesis. Methods In order to provide a tumor-targeted delivery carrier of siRNA in cancer therapy, the hyaluronic acid (HA)-selenium (Se)-polyethylenimine (PEI) nanoparticle (NP) was fabricated by decorating SeNP with HA as a tumor-targeting moiety and by linking the polycationic polymers polyethylenimine PEI onto the surface of SeNP. The siRNA was loaded to the surface of SeNP HA-Se-PEI via the electrostatic interaction between siRNA and PEI to prepare the functionalized SeNP HA-Se-PEI@siRNA. Results The HA-Se-PEI@siRNA was internalized into the HepG2 cell mainly in a clathrin-mediated endocytosis manner. Owing to the active tumor-targeted effect mediated by HA, HA-Se-PEI@siRNA achieved the obvious higher transfection efficiency, greater gene silencing ability, and stronger cytotoxicity in the HepG2 cell compared with the passive tumor-targeted NP Se-PEI@siRNA. The knockdown of hairy and enhancer of split 5 by HA-Se-PEI@siRNA induced the HepG2 cell cycle arrest at the G0/G1 phase and apoptosis. Furthermore, the treatment with HA-Se-PEI@siRNA resulted in greater antitumor efficacy compared with the Se-PEI@siRNA in vitro and in vivo. In addition, the HA-Se-PEI@siRNA was almost no toxic to the key organs of mice. Conclusion These findings provided an alternative therapeutic route for targeted cancer treatments.

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“…VEGF delivery using an inorganic gold NP containing VEGF siRNA repressed tumor revascularization in HCC in vitro and in vivo ( 48 ). In another case, a polymer NP complex was used to transport VEGF siRNA and demonstrated a marked anti-angiogenic effect in vitro and in vivo ( 49 ). An alternate siRNA design involved methylation of VEGF siRNA ends to stabilize them in vivo and this therapy reduced HCC induced angiogenesis through inactivation of VEGF/PI3K/AKT signaling pathway ( 46 ).…”

Section: Rnai Strategiesmentioning

confidence: 99%

RNA Therapeutic Options to Manage Aberrant Signaling Pathways in Hepatocellular Carcinoma: Dream or Reality?

et al. 2022

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Despite the early promise of RNA therapeutics as a magic bullet to modulate aberrant signaling in cancer, this field remains a work-in-progress. Nevertheless, RNA therapeutics is now a reality for the treatment of viral diseases (COVID-19) and offers great promise for cancer. This review paper specifically investigates RNAi as a therapeutic option for HCC and discusses a range of RNAi technology including anti-sense oligonucleotides (ASOs), Aptamers, small interfering RNA (siRNA), ribozymes, riboswitches and CRISPR/Cas9 technology. The use of these RNAi based interventions is specifically outlined in three primary strategies, namely, repressing angiogenesis, the suppression of cell proliferation and the promotion of apoptosis. We also discuss some of the inherent chemical and delivery problems, as well as targeting issues and immunogenic reaction to RNAi interventions.

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Polyethylene glycol–poly(ε-benzyloxycarbonyl-L-lysine)-conjugated VEGF siRNA for antiangiogenic gene therapy in hepatocellular carcinoma

Cited by 26 publications

References 43 publications

Lipid and Polymer-Based Nanoparticle siRNA Delivery Systems for Cancer Therapy

Lipid and Polymer-Based Nanoparticle siRNA Delivery Systems for Cancer Therapy

siRNA-loaded selenium nanoparticle modified with hyaluronic acid for enhanced hepatocellular carcinoma therapy

RNA Therapeutic Options to Manage Aberrant Signaling Pathways in Hepatocellular Carcinoma: Dream or Reality?

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