Cationic Liposomal Co-delivery of Small Interfering RNA and a MEK Inhibitor for Enhanced Anticancer Efficacy

Kang, Sung Soo; Cho, Hee Jeong; Shim, Gayong; Lee, Sangbin; Kim, Su Hyeon; Choi, Han Gon; Kim, Chan Wha; Oh, Yu‐Kyoung

doi:10.1007/s11095-011-0569-4

Cited by 56 publications

(27 citation statements)

References 31 publications

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“…Furthermore, the combination of PTX and siRNA in CLP suppressed the Bcap-37cancer cells more potently. This result was similar to the report by Kang et al 38 Above all, we can conclude that the codelivery system has a significantly higher cytotoxicity in vitro than liposomal PTX or siRNA alone. The data indicated that CLP codelivery of MRP1-siRNA and PTX could silence the MRP1 mRNA and significantly suppress the pump resistance, which indirectly improved the intracellular concentration of PTX drug and thus resulted in a better anticancer effect.…”

Section: Apoptotic Effect Of Clp Complexes and Molecular Level Evaluasupporting

confidence: 92%

Codelivery of paclitaxel and small interfering RNA by octadecyl quaternized carboxymethyl chitosan-modified cationic liposome for combined cancer therapy

et al. 2015

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Conventional therapeutic approaches for cancer are limited by cancer cell resistance, which has impeded their clinical applications. The main goal of this work was to investigate the combined antitumor effect of paclitaxel with small interfering RNA modified by cationic liposome formed from modified octadecyl quaternized carboxymethyl chitosan. The cationic liposome was composed of 3β-[N-(N', N'-dimethylaminoethane)-carbamoyl]-cholesterol, dioleoylphosphatidylethanolamine, and octadecyl quaternized carboxymethyl chitosan. The cationic liposome properties were characterized by Fourier transform infrared spectroscopy, dynamic light scattering and zeta potential measurements, transmission electron microscopy, atomic force microscopy, and gel retardation assay. The cationic liposome exhibited good properties, such as a small particle size, a narrow particle size distribution, a good spherical shape, a smooth surface, and a good binding ability with small interfering RNA. Most importantly, when combined with paclitaxel and small interfering RNA, the composite cationic liposome induced a great enhancement in the antitumor activity, which showed a significantly higher in vitro cytotoxicity in Bcap-37 cells than liposomal paclitaxel or small interfering RNA alone. In conclusion, the results indicate that cationic liposome could be further developed as a codelivery system for chemotherapy drugs and therapeutic small interfering RNAs.

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Section: Apoptotic Effect Of Clp Complexes and Molecular Level Evaluasupporting

confidence: 92%

Codelivery of paclitaxel and small interfering RNA by octadecyl quaternized carboxymethyl chitosan-modified cationic liposome for combined cancer therapy

et al. 2015

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“…The in vivo effects of the siRNA PDGL complex in KB epithelial cancer cell bearing mice revealed that Mcl1 levels and pERK1/2 levels were significantly decreased by siMcl1 and MEK inhibitor PD0325901. The treatment of mice with siMcl1 complexed with PDGL resulted in significant decrease in tumor size by 79% compared to control group [143]. …”

Section: Nanotechnology Based Approaches To Deliver Rnai Based Commentioning

confidence: 99%

Nanocarrier mediated delivery of siRNA/miRNA in combination with chemotherapeutic agents for cancer therapy: Current progress and advances

Gandhi

Tekade

Chougule

2014

Journal of Controlled Release

328

270

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Chemotherapeutic agents have certain limitations when it comes to treating cancer, the most important being severe side effects along with multidrug resistance developed against them. Tumor cells exhibits drug resistance due to activation of various cellular level processes viz. activation of drug efflux pumps, anti-apoptotic defense mechanisms etc. Currently, RNA interference (RNAi) based therapeutic approaches are under vibrant scrutinization to seek cancer cure. Especially small interfering RNA (siRNA) and micro RNA (miRNA), are able to knock down the carcinogenic genes by targeting the mRNA expression, which underlies the uniqueness of this therapeutic approach. Recent research focus in the regime of cancer therapy involves the engagement of targeted delivery of siRNA/miRNA in combinations with other therapeutic agents (such as gene, DNA or chemotherapeutic drug) for targeting permeability glycoprotein (P-gp), Multidrug resistant protein 1(MRP-1), B-cell lymphoma (BCL-2) and other targets that are mainly responsible for resistance in cancer therapy. RNAi-chemotherapeutic drug combinations have also been found to be effective against different molecular targets as well and can increase the sensitization of cancer cells to therapy several folds. However, due to stability issues associated with siRNA/miRNA suitable protective carrier is needed and nanotechnology based approaches have been widely explored to overcome these drawbacks. Furthermore, it has been univocally advocated that the co-delivery of siRNA/miRNA with other chemodrugs significantly enhances their capability to overcome cancer resistance compared to naked counterparts. The objective of this article is to review recent nanocarrier based approaches adopted for the delivery of siRNA/miRNA combinations with other anticancer agents (siRNA/miRNA/pDNA/chemodrugs) to treat cancer.

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“…The co-delivery liposomes realized enhanced tumor targeting, better control of tumor volume and inhibition of neovascularization on mice-bearing MCF-7 in situ breast tumor [61] MEK inhibitor PD0325901 and MCL1 siRNA Cationic liposome -The co-delivery liposomes achieved remarkable improvement in the inhibition of tumor growth on xenograft mice model, compared with single agent-loaded liposomes [62] Docetaxel and BCL-2 siRNA Pegylated cationic liposome -Treatment with the co-delivery liposomes resulted in a significant reduction in tumor volume of the mice-bearing A549 cell xenograft tumor and a 100% survival rate in 25 days [63] Mitoxantrone (MTO) and…”

Section: Vapreotidementioning

confidence: 99%

“…The co-delivery system realized inhibition of tumor growth and neovascularization on mice-bearing MCF-7 in situ breast tumor. Kang et al coformulated hydrophobic small molecule MEK inhibitor PD0325901 and siRNA targeting MCL1 in N′,N′′-dioleylglutamide (DG)-based cationic liposomes for the treatment of cancer [62]. PD0325901-loaded cationic liposomes (PDGL) were synthesized by drying PD0325901, DG, DOPE and cholesterol from organic solvent followed by hydration and extrusion.…”

Section: Lipid-based Nanocarriers Liposomesmentioning

confidence: 99%

Nanocarriers for Delivery of siRNA and Co-Delivery of siRNA and Other Therapeutic Agents

Zhao

Feng

2015

Nanomedicine (Lond.)

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A major problem in cancer treatment is the multidrug resistance. siRNA inhibitors have great advantages to solve the problem, if the bottleneck of their delivery could be well addressed by the various nanocarriers. Moreover, co-delivery of siRNA together with the various anticancer agents in one nanocarrier may maximize their additive or synergistic effect. This review provides a comprehensive summary on the state-of-the-art of the nanocarriers, which may include prodrugs, micelles, liposomes, dendrimers, nanohydrogels, solid lipid nanoparticles, nanoparticles of biodegradable polymers and nucleic acid nanocarriers for delivery of siRNA and co-delivery of siRNA together with anticancer agents with focus on synthesis of the nanocarrier materials, design and characterization, in vitro and in vivo evaluation, and prospect and challenges of nanocarriers.

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Cationic Liposomal Co-delivery of Small Interfering RNA and a MEK Inhibitor for Enhanced Anticancer Efficacy

Abstract: PDGL-mediated co-delivery of siMcl1 and MEK inhibitor, PD0325901, could serve as a potential strategy for combination chemogene anticancer therapy.

Cited by 56 publications

References 31 publications

Codelivery of paclitaxel and small interfering RNA by octadecyl quaternized carboxymethyl chitosan-modified cationic liposome for combined cancer therapy

Codelivery of paclitaxel and small interfering RNA by octadecyl quaternized carboxymethyl chitosan-modified cationic liposome for combined cancer therapy

Nanocarrier mediated delivery of siRNA/miRNA in combination with chemotherapeutic agents for cancer therapy: Current progress and advances

Nanocarriers for Delivery of siRNA and Co-Delivery of siRNA and Other Therapeutic Agents

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