Novel Lipoidal amine-based Nanocarrier Formulations for siRNA Delivery

Zhou, Chenguang; Zhang, Yue; Lee, L James; Lee, Robert J.

doi:10.4155/tde.12.47

Cited by 3 publications

(1 citation statement)

References 30 publications

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“…26–28 Efficient delivery of siRNA requires functional synergy between cellular uptake, vesicular trafficking, vesicular escape, unpacking of NCs, and cytoplasmic release of siRNA. 29 The cellular entry pathway and cellular pharmacokinetics determine the magnitude and duration of the siRNA exposure for the intracellular target, and ultimately govern the RNAi response.…”

Section: Discussionmentioning

confidence: 99%

Comparative cellular pharmacokinetics and pharmacodynamics of siRNA delivery by SPANosomes and by cationic liposomes

Zhou

Zhang

et al. 2013

Nanomedicine: Nanotechnology, Biology and Medicine

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Mechanistic understanding of intracellular trafficking is important for the development of small interfering RNA (siRNA) delivery vehicles. Here, we describe a novel methodology to quantitatively analyze nanocarrier-mediated disposition of siRNA. Cellular uptake and cytoplasmic release of siRNA over time were quantified by measuring the fluorescence intensities of fluorescently-labeled siRNAs and molecular beacons using flow cytometry. This method was used to investigate the cellular pharmacokinetics (PK) of siRNA delivery by SPANosomes (SP) and by cationic liposomes (CL). The results showed that the superior pharmacodynamic (PD) response of SP was because it enhanced transport of siRNA into the cytoplasm compared to the CL. The divergent cellular pharmacokinetic profiles of the two formulations were associated with different cellular entry pathways. These findings can facilitate the rational design of more efficient siRNA delivery vehicles in the future.

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Section: Discussionmentioning

confidence: 99%

Comparative cellular pharmacokinetics and pharmacodynamics of siRNA delivery by SPANosomes and by cationic liposomes

Zhou

Zhang

et al. 2013

Nanomedicine: Nanotechnology, Biology and Medicine

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Nanoparticle‐Mediated siRNA Delivery and Multifunctional Modification Strategies for Effective Cancer Therapy

Chen

Dong

Shi

2021

Adv Materials Technologies

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method clinically, however, it is accompanied by the inevitable side effects on normal tissues. [9] Similarly, other treatment methods have failed to achieve satisfactory treatment results in clinic. With the discovery of key oncogenic markers and pathways, gene therapy has become a novel class of pharmaceutical drugs and shown significant therapeutic advantages in fighting cancer. [10][11][12] Compared with chemotherapy, gene therapy has better selectivity and specificity for related genes.RNA interference (RNAi) is an important defense mechanism of eukaryotic cells, which inhibits the expression or transcription of specific genes by blocking their translation or transcription, so it is considered to be a revolutionary tool for mediating gene therapy. [13][14][15] Previous research has shown that RNAi can effectively modulating the expression of any gene involved in tumor initiation, growth, and metastasis formation. [16][17][18] MicroRNA (miRNA), small interfering RNA (siRNA), and short hairpin RNA (shRNA) are the major types of RNAi molecules, which can mediate RNAi and cause mRNA cleavage. [19] miRNA is an endogenous single-stranded RNA, which mainly acts on the 3'-untranslated region of target genes in the RNAi pathway. [20] While siRNA is a double-stranded RNA (dsRNA) which can be transfected into the human body and act on any part of mRNA. [21] shRNA can be cloned into an expression vector and express siRNA. [22] siRNA has powerful specific RNAi triggering activity, so it shows great potential in nucleic acid therapy. [23] siRNA is a 20-25 base pair nucleic acid fragment that can degrade messenger RNA (mRNA) in the cytoplasm and interfere with the expression of specific genes. [24][25][26] The mechanism of siRNA-mediated RNAi action is shown in Figure 1. siRNA is synthesized and delivered into the cytoplasm, or generated by the endogenous Dicer-mediated dsRNA cleavage, then it can be incorporated into the RNA-induced silencing complex (RISC, a multi-protein complex). Then the sense strand (nonguiding strand) is cleaved by the Argonaute 2 (AGO2, an endonuclease of the RISC), while the antisense strand guides RISC toward the target mRNA with a complementary sequence, which is further cleaved by AGO2 into mRNA fragments. Subsequently, the mRNA fragments are degraded by cellular exonuclease. In addition, the antisense strand-RISC complex is capable of being recycled, so effectively preventing the translation of target mRNA into proteins.RNA interference (RNAi), which can inhibit the expression or transcription of specific genes, is considered to be a revolutionary tool for mediating gene therapy. Small interfering RNA (siRNA) is an important therapeutic agent for RNAi. However, the clinical application of siRNA-based gene silencing is still limited due to the easy degradation of siRNA during the circulation in the body and the difficulty in delivering siRNA to desired tissues and cells. The rapid development of nanotechnology provides new ideas for siRNA delivery and a large variety of nanocarriers have been d...

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Fatty acid modified octa-arginine for delivery of siRNA

Wang

et al. 2015

International Journal of Pharmaceutics

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Novel Lipoidal amine-based Nanocarrier Formulations for siRNA Delivery

Abstract: Background-Lack of safe and efficient delivery of siRNA remains the greatest hurdle for the therapeutic application of siRNA. This article reports synthesis and evaluation of novel lipoidal amine-based nanocarrier (LANC) formulations for siRNA delivery.

Cited by 3 publications

References 30 publications

Comparative cellular pharmacokinetics and pharmacodynamics of siRNA delivery by SPANosomes and by cationic liposomes

Comparative cellular pharmacokinetics and pharmacodynamics of siRNA delivery by SPANosomes and by cationic liposomes

Nanoparticle‐Mediated siRNA Delivery and Multifunctional Modification Strategies for Effective Cancer Therapy

Fatty acid modified octa-arginine for delivery of siRNA

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