Evaluation of dendrimer type bio-reducible polymer as a siRNA delivery carrier for cancer therapy

Nam, Joung Pyo; Nam, Ki Woong; Jung, Simhyun; Nah, Jae Woon; Kim, Sung Wan

doi:10.1016/j.jconrel.2015.04.039

Cited by 41 publications

(22 citation statements)

References 34 publications

(45 reference statements)

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“…Nam et al . evaluated an arginine-grafted, bioreducible poly(cystaminebisacrylamide-diaminohexane), called ABP, and PAMAM (PAM-ABP) for delivering anti-VEGF siRNA to various cancer types, including hepatocarcinoma, lung adenocarcinoma, and fibrosarcoma, in vitro [85]. Interestingly, their PAM-ABP dendrimer showed better gene silencing efficiency than did PEI/siRNA polyplexes.…”

Section: Polymeric Nanoparticles In Sirna Deliverymentioning

confidence: 99%

Nanoparticles for siRNA-Based Gene Silencing in Tumor Therapy

Babu

Muralidharan

Amreddy

et al. 2016

IEEE Trans.on Nanobioscience

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Gene silencing through RNA interference (RNAi) has emerged as a potential strategy in manipulating cancer causing genes by complementary base-pairing mechanism. Small interfering RNA (siRNA) is an important RNAi tool that has found significant application in cancer therapy. However due to lack of stability, poor cellular uptake and high probability of loss-of-function due to degradation, siRNA therapeutic strategies seek safe and efficient delivery vehicles for in vivo applications. The current review discusses various nanoparticle systems currently used for siRNA delivery for cancer therapy, with emphasis on liposome based gene delivery systems. The discussion also includes various methods availed to improve nanoparticle based-siRNA delivery with target specificity and superior efficiency. Further this review describes challenges and perspectives on the development of safe and efficient nanoparticle based-siRNA-delivery systems for cancer therapy.

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Section: Polymeric Nanoparticles In Sirna Deliverymentioning

confidence: 99%

Nanoparticles for siRNA-Based Gene Silencing in Tumor Therapy

Babu

Muralidharan

Amreddy

et al. 2016

IEEE Trans.on Nanobioscience

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“…3,4 Polyamidoamine (PAMAM) dendrimers are a class of synthetic polymers with well-defined structure and molecular weight. To achieve both high efficacy and low toxicity, PAMAM dendrimers of different generations were modified with cyclodextrins, 15,16 arginine, 17,18 peptides, 19 fluorous compounds, 20 polymers, 21,22 and nanomaterials. [8][9][10][11] In a pioneering study, high generation dendrimers such as generation 7 (G7) PAMAM dendrimer with a triethanolamine core efficiently induce endogenous gene silencing.…”

Section: Introductionmentioning

confidence: 99%

Efficient delivery of small interfering RNA into cancer cells using dodecylated dendrimers

Chang

Zhang

et al. 2015

J. Mater. Chem. B

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Polyamidoamine (PAMAM) dendrimers are promising nonviral gene vectors due to their well-defined molecular structure, low immune response and ease of modification. High generation PAMAM dendrimers are reported with relatively high efficacy in the delivery of small interfering RNA (siRNA), but are suffering from several drawbacks such as severe cytotoxicity and high cost of manufacturing. Here, we report several efficient siRNA vectors based on low generation dendrimers. Dodecylated G2, G3 and G4 PAMAM dendrimers show dramatically increased gene silencing efficiency with negligible cytotoxicity on several cell lines compared to unmodified dendrimers. The increased gene silencing efficacy is mainly attributed to the hydrophobic modification on the dendrimer surface which significantly increases the cellular uptake of dendrimer/siRNA complexes. In addition, the most efficient polymer G4-23C12 can also efficiently deliver Bcl-2 siRNA into cancer cells, specifically inhibit the expression of target gene in vitro, and further lead to cell apoptosis. This study reveals the structure-function relationship of lipid-modified dendrimers in siRNA delivery and provides valuable insight to guide the development of efficient and non-toxic siRNA vectors.

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“…Studies have shown, the KSP siRNA can lead to the generation of a single star spindle promote mitotic arrest in M phase and induce apoptosis of tumor cells [14] . [15] , the body's normal proliferation of cells, there are also the expression of KSP, but its expression level was significantly lower than the malignant tissue; the body's normal differentiation and maturation of cells and tissues, such as nerve cells were not detected in the KSP expression [16] .…”

Section: Discussionmentioning

confidence: 99%

Downregulation of VEGF and KSP Gene Expression Inhibits Proliferation of A549 Cells

Hu¹

2016

ijSciences

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Abstract:To investigate the proliferation and invasion of A549 cell by down-regulating KSP and VEGF gene.Designing and screening the siRNA of targeting VEGF and KSP promoter, transfected into A549 cells with transfetion reagent. According to the difference of transfection mixture the cells were divided into five groups.Western Blotting was used to detect the expression of VEGF and KSP. MTT assay was used to detect the cell proliferation, qPCR was used to measure the expression of VEGF and KSP, the MTT results indicated that the proliferation of the cells was significantly decreased; The results of qPCR showed that the siRNA obviously decreased the expression of VEGF and KSP gene;. The Western Blotting showed that the expression of VEGF and KSP were significantly reduced; The proliferation of the co-transfected cell were inhibited more than the single group transfected cell. These results indicate that co-regulation of VEGF and KSP gene expression more effectively inhibit A549 cell proliferation, better than only regulating VEGF or KSP gene expression.

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Evaluation of dendrimer type bio-reducible polymer as a siRNA delivery carrier for cancer therapy

Cited by 41 publications

References 34 publications

Nanoparticles for siRNA-Based Gene Silencing in Tumor Therapy

Nanoparticles for siRNA-Based Gene Silencing in Tumor Therapy

Efficient delivery of small interfering RNA into cancer cells using dodecylated dendrimers

Downregulation of VEGF and KSP Gene Expression Inhibits Proliferation of A549 Cells

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