The synergistic effect of hierarchical assemblies of siRNA and chemotherapeutic drugs co-delivered into hepatic cancer cells

Cao, Nuo; Cheng, Du; Zou, Seyin; Ai, Hua; Gao, Jinming; Shuai, Xintao

doi:10.1016/j.biomaterials.2010.11.061

Cited by 211 publications

(167 citation statements)

References 40 publications

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“…16 Skov-3 human ovarian cancer cell line overexpressing surface receptors for FA was obtained from the Cell Bank of Shanghai Institutes for Biological Sciences (Shanghai, China). Two siRNA duplexes, designed to target Bcl-2 gene using algorithms from public software, were provided by Genpharm (Shanghai, China).…”

Section: Materials and Methods Materialsmentioning

confidence: 99%

“…On the other hand, complex based on PEG-PEI-PCL is believed to possess a better stability than that based on a hierarchical multilayer assembly, in which PEG coating of polyplex was achieved upon electrostatic interaction, rather than covalent linkage. 16 …”

Section: Introductionmentioning

confidence: 99%

“…15,16 On the other hand, it has been proven that nano-based chemotherapeutics improve the efficacy of drugs, lessen toxicity to normal tissue, and improve patient compliance rate. 17 A recent advance in nanomedicine for cancer therapy is the development of multifunctional nanocarriers, which may jointly deliver chemotherapeutic drugs and genes or siRNA.…”

Section: Introductionmentioning

confidence: 99%

“…Therefore, delivery of nanocarriers into these cells can be enhanced using the folate-directed targeting strategy. 16 Herein, we developed a folate-targeted, multifunctional nanocarrier for codelivering DOX and siRNA targeting the Bcl-2 gene (Bcl-2 siRNA) into ovarian cancer cells overexpressing receptors for folic acid (FA), in the hope of suppressing drug resistance, thereby enhancing apoptosis of cancer cells in DOX treatment. The nanocarrier was prepared based on a triblock copolymer (PEG-PEI-PCL) of poly(ethylene glycol) (PEG), poly(ethylene imine) (PEI), and poly(ε-caprolactone) (PCL).…”

Section: Introductionmentioning

confidence: 99%

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Enhanced apoptosis of ovarian cancer cells via nanocarrier-mediated codelivery of siRNA and doxorubicin

Shuai¹

2012

IJN

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A folate conjugated ternary copolymer, FA-PEG-PEI-PCL, of poly(ethylene glycol) (PEG), poly(ethylene imine) (PEI), and poly(ε-caprolactone) (PCL) was synthesized. The copolymer self-assembled into cationic micelles capable of co-delivering siRNA and the anticancer drug doxorubicin (DOX). This dual functional nanocarrier demonstrated low cytotoxicity and high performance in drug/siRNA delivery. Upon the codelivery of siRNA, targeting the Bcl-2 gene, and DOX, using the folate-targeted nanocarrier, DOX-induced apoptosis in the skov-3 cells overexpressing folate receptor was significantly enhanced through a mechanism of downregulating the antiapoptotic protein Bcl-2, while simultaneously upregulating the proapoptotic protein Bax. This work suggested that the combination of Bcl-2 siRNA and DOX therapies is feasible, based on our dual functional nanocarrier, which set up a good basis for a future in vivo test.

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Section: Materials and Methods Materialsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Enhanced apoptosis of ovarian cancer cells via nanocarrier-mediated codelivery of siRNA and doxorubicin

Shuai¹

2012

IJN

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“…43 The pH of the solution was regulated to 8-9 by adding 5% NaOH solution. After being stirred for another 2 h, the resulting solution was filtered through a 0.22 µm Millipore filter to obtain siRNA-PTX/LDL-NSC-SS-UA micelles.…”

Section: Rnase Protection Assay and Serum Stabilitymentioning

confidence: 99%

Low-density lipoprotein-coupled micelles with reduction and pH dual sensitivity for intelligent co-delivery of paclitaxel and siRNA to breast tumor

Zhu¹,

Yang²,

Qu³

et al. 2017

IJN

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Multidrug resistance (MDR) is a major obstacle for the clinical therapy of malignant human cancers. The discovery of RNA interference provides efficient gene silencing within tumor cells for reversing MDR. In this study, a new “binary polymer” low-density lipoprotein– N -succinyl chitosan–cystamine–urocanic acid (LDL–NSC–SS–UA) with dual pH/redox sensitivity and targeting effect was synthesized for the co-delivery of breast cancer resistance protein small interfering RNA (siRNA) and paclitaxel (PTX). In vivo, the co-delivering micelles can accumulate in tumor tissue via the enhanced permeability and retention effect and the specific recognition and combination of LDL and LDL receptor, which is overexpressed on the surface of tumor cell membranes. The siRNA–PTX-loaded micelles inhibited gene and drug release under physiological conditions while promoting fast release in an acid microenvironment or in the presence of glutathione. The micelles escaped from the lysosome through the proton sponge effect. Additionally, the micelles exhibited superior antitumor activity and downregulated the protein and mRNA expression levels of breast cancer resistance protein in MCF-7/Taxol cells. The biodistribution and antitumor studies proved that the siRNA–PTX-loaded micelles possessed prolonged circulation time with a remarkable tumor-targeting effect and effectively inhibited tumor growth. Therefore, the novel dual pH/redox-sensitive polymers co-delivering siRNA and PTX with excellent biocompatibility and effective reversal of MDR demonstrate a considerable potential in cancer therapy.

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Multifunctional Polymeric Nanosystems forRNAInterference Therapy

Iyer¹,

Ganesh²,

Zhou³

et al. 2013

Pharmaceutical Sciences Encyclopedia

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RNA interference (RNAi) is one of the most powerful tools for selective silencing of specific aberrant genes for therapeutic management of diseases such as cancer, diabetes, and inflammatory disorders. However, the labile nature of nucleic acid constructs coupled with the difficulty in selectively delivering them to the target tissues, cells, and the intracellular cellular machinery within the cells has been a primary hindrance for the clinical translation of RNAi. Multifunctional nano‐systems provide distinct advantages over other delivery strategies based on their ability to selectively target diseased tissues, such as solid tumors based on passive and active targeting principles. Such nano‐systems can incorporate multiple therapeutic payloads, such as small molecule drugs, small interfering RNAs (siRNAs), and micro RNAs (miRNAs) as well as imaging/contrast agents for simultaneous disease detection, quantifying siRNA/miRNA gene expression/knockdown, examining in vivo fate and sites of localization/excretion, as well as exploring therapeutic potentials in vivo. In this chapter, we have described the principles and mechanisms based on RNA interference phenomenon and the barriers to its successful clinical translation. Furthermore, we have discussed the modes of delivery that have been employed including the advantages of multifunctional polymeric nano‐systems with illustrative examples covering their utility in the management of diseases such as cancer, inflammation, and other chronic diseases.

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The synergistic effect of hierarchical assemblies of siRNA and chemotherapeutic drugs co-delivered into hepatic cancer cells

Cited by 211 publications

References 40 publications

Enhanced apoptosis of ovarian cancer cells via nanocarrier-mediated codelivery of siRNA and doxorubicin

Enhanced apoptosis of ovarian cancer cells via nanocarrier-mediated codelivery of siRNA and doxorubicin

Low-density lipoprotein-coupled micelles with reduction and pH dual sensitivity for intelligent co-delivery of paclitaxel and siRNA to breast tumor

Multifunctional Polymeric Nanosystems forRNAInterference Therapy

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