Co-Delivery of Gemcitabine and Mcl-1 SiRNA via Cationic Liposome-Based System Enhances the Efficacy of Chemotherapy in Pancreatic Cancer

Wang, Yanbing; Gao, Fenghua; Jiang, Xingwei; Zhao, Xiao; Wang, Yu; Kuai, Qiyuan; Nie, Guangjun; He, Min; Pan, Yingjie; Shi, Wei; Ren, Suping; Yu, Qun

doi:10.1166/jbn.2019.2762

Cited by 37 publications

(13 citation statements)

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“…These cationic liposomes were also functionalized with a targeting aptamer (AS1411) to further enhance tumor accumulation [54]. In another report, the use of gemcitabine (Gem) in combination with Myeloid cell leukemia 1 (MCL1)-targeting siRNA in loaded liposomes was shown to be effective in treating pancreatic cancer [55]. These experimental examples suggest that the use of siRNAs targeting specific oncogenes over-expressed in cancer cells are able to synergize with chemotherapy, resulting in reduced tumor growth in a wide variety of xenograft tumor models.…”

Section: Liposomesmentioning

confidence: 99%

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: Liposomesmentioning

confidence: 99%

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

2020

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“…Lipids or lipid-like materials (lipidoids) are able to form various vesicles, e.g., LNP, liposome, lipid emulsion, lipid implant, with nuclei acids [ 3 , [7] , [8] , [9] , [10] , [11] ]. A series of cationic lipids and ionizable lipids such as 1,2-dioleoyloxy-3-trimethylammonium propane chloride (DOTAP), N-[1-(2,3-dioleoyloxy) propyl]-N,N,N-trimethylammo- nium chloride (DOTMA), 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine (DOPE), dilinoleylmethyl-4-dimethylaminobutyrate (Dlin-MC3-DMA) have been investigated for siRNA or mRNA delivery [ 5 , 10 , [12] , [13] , [14] , [15] , [16] , [17] ]. Ionizable LNP (iLNP) is more clinically advanced than other deliver systems in the context of RNA delivery.…”

Section: Introductionmentioning

confidence: 99%

Efficient hepatic delivery and protein expression enabled by optimized mRNA and ionizable lipid nanoparticle

Yang

Wang

et al. 2020

Bioactive Materials

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mRNA is a novel class of therapeutic modality that holds great promise in vaccination, protein replacement therapy, cancer immunotherapy, immune cell engineering etc. However, optimization of mRNA molecules and efficient in vivo delivery are quite important but challenging for its broad application. Here we present an ionizable lipid nanoparticle (iLNP) based on iBL0713 lipid for in vitro and in vivo expression of desired proteins using codon-optimized mRNAs. mRNAs encoding luciferase or erythropoietin (EPO) were prepared by in vitro transcription and formulated with proposed iLNP, to form iLP171/mRNA formulations. It was revealed that both luciferase and EPO proteins were successfully expressed by human hepatocellular carcinoma cells and hepatocytes. The maximum amount of protein expression was found at 6 h post-administration. The expression efficiency of EPO with codon-optimized mRNA was significantly higher than that of unoptimized mRNA. Moreover, no toxicity or immunogenicity was observed for these mRNA formulations. Therefore, our study provides a useful and promising platform for mRNA therapeutic development.

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“…Liposomes demonstrated high cellular uptake, resulting in Mcl-1 down-regulation as a tumor-promoting factor for PC cells. Thus, sensitivity of PC cells toward GEM increased and an increase occurred in the number of PC cells undergoing apoptosis [ 247 ].…”

Section: Co-delivery Systemsmentioning

confidence: 99%

Pre-Clinical and Clinical Applications of Small Interfering RNAs (siRNA) and Co-Delivery Systems for Pancreatic Cancer Therapy

Mirzaei

Gholami

Ang

et al. 2021

Cells

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Pancreatic cancer (PC) is one of the leading causes of death and is the fourth most malignant tumor in men. The epigenetic and genetic alterations appear to be responsible for development of PC. Small interfering RNA (siRNA) is a powerful genetic tool that can bind to its target and reduces expression level of a specific gene. The various critical genes involved in PC progression can be effectively targeted using diverse siRNAs. Moreover, siRNAs can enhance efficacy of chemotherapy and radiotherapy in inhibiting PC progression. However, siRNAs suffer from different off target effects and their degradation by enzymes in serum can diminish their potential in gene silencing. Loading siRNAs on nanoparticles can effectively protect them against degradation and can inhibit off target actions by facilitating targeted delivery. This leads to enhanced efficacy of siRNAs in PC therapy. Moreover, different kinds of nanoparticles such as polymeric nanoparticles, lipid nanoparticles and metal nanostructures have been applied for optimal delivery of siRNAs that are discussed in this article. This review also reveals that how naked siRNAs and their delivery systems can be exploited in treatment of PC and as siRNAs are currently being applied in clinical trials, significant progress can be made by translating the current findings into the clinical settings.

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Co-Delivery of Gemcitabine and Mcl-1 SiRNA via Cationic Liposome-Based System Enhances the Efficacy of Chemotherapy in Pancreatic Cancer

Cited by 37 publications

References 0 publications

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

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

Efficient hepatic delivery and protein expression enabled by optimized mRNA and ionizable lipid nanoparticle

Pre-Clinical and Clinical Applications of Small Interfering RNAs (siRNA) and Co-Delivery Systems for Pancreatic Cancer Therapy

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