Key determinants of siRNA delivery mediated by unique pH-responsive lipid-based liposomes

Sako, Mariko; Furan, Song; Okamoto, Ai; Koide, Hiroyuki; Dewa, Takehisa; Oku, Naoto; Asai, Tomohiro

doi:10.1016/j.ijpharm.2019.118606

Cited by 15 publications

(13 citation statements)

References 31 publications

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“…cGQDs, carboxylated graphene quantum dots, entered human cervical cancer cells mainly through the macropinocytosis-dependent pathway and showed outstanding antitumor ability and low systemic toxicity (180). DOP-DETAbased liposomes, a special lipid derivative response to pH, could transmit siRNA through macropinocytosis, and mediate RNA interference under low siRNA conditions (181). In addition, PCLs, plier-like cationic liposomes, was found primarily internalized through macropinocytosis, thus, have great prospects as alternative effective gene delivery systems (182).…”

Section: Othersmentioning

confidence: 99%

The Dual Role of Macropinocytosis in Cancers: Promoting Growth and Inducing Methuosis to Participate in Anticancer Therapies as Targets

et al. 2021

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Macropinocytosis is an important mechanism of internalizing extracellular materials and dissolved molecules in eukaryotic cells. Macropinocytosis has a dual effect on cancer cells. On the one hand, cells expressing RAS genes (such as K-RAS, H-RAS) under the stress of nutrient deficiency can spontaneously produce constitutive macropinocytosis to promote the growth of cancer cells by internalization of extracellular nutrients (like proteins), receptors, and extracellular vesicles(EVs). On the other hand, abnormal expression of RAS genes and drug treatment (such as MOMIPP) can induce a novel cell death associated with hyperactivated macropinocytosis: methuosis. Based on the dual effect, there is immense potential for designing anticancer therapies that target macropinocytosis in cancer cells. In view of the fact that there has been little review of the dual effect of macropinocytosis in cancer cells, herein, we systematically review the general process of macropinocytosis, its specific manifestation in cancer cells, and its application in cancer treatment, including anticancer drug delivery and destruction of macropinocytosis. This review aims to serve as a reference for studying macropinocytosis in cancers and designing macropinocytosis-targeting anticancer drugs in the future.

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Section: Othersmentioning

confidence: 99%

The Dual Role of Macropinocytosis in Cancers: Promoting Growth and Inducing Methuosis to Participate in Anticancer Therapies as Targets

et al. 2021

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“…A dioleylphosphate-diethylenetriamine conjugate (DOP-DETA) which consists of a pH-responsive triamine and unsaturated fatty acid was designed and accelerated membrane fusion. This kind of liposome was proved to deliver siRNA into the cytoplasm with high efficiency and induce silencing efficiency at a low siRNA concentration ( Sako et al, 2019 ).…”

Section: Challenges and Strategiesmentioning

confidence: 99%

Rationale and Application of PEGylated Lipid-Based System for Advanced Target Delivery of siRNA

Chen

Zhao

et al. 2021

Front. Pharmacol.

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RNA interference (RNAi) technology has become a powerful tool in application of unraveling the mechanism of disease and may hold the potential to be developed for clinical uses. Small interfering RNA (siRNA) can bind to target mRNA with high specificity and efficacy and thus inhibit the expression of related protein for the purpose of treatment of diseases. The major challenge for RNAi application is how to improve its stability and bioactivity and therefore deliver therapeutic agents to the target sites with high efficiency and accuracy. PEGylated lipid-based delivery system has been widely used for development of various medicines due to its long circulating half-life time, low toxicity, biocompatibility, and easiness to be scaled up. The PEGylated lipid-based delivery system may also provide platform for targeting delivery of nucleic acids, and some of the research works have moved to the phases for clinical trials. In this review, we introduced the mechanism, major challenges, and strategies to overcome technical barriers of PEGylated lipid-based delivery systems for advanced target delivery of siRNA in vivo. We also summarized recent advance of PEGylated lipid-based siRNA delivery systems and included some successful research works in this field.

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“…In addition to the p K a of the ionizable lipid, the lipid composition of LNPs and the molar ratio of siRNA and lipids in LNPs affects the efficiency of siRNA delivery [ 25 , 26 , 31 ]. The design of an appropriate formulation of LNPs must be required to capture siRNA in LNPs and induce efficient endosomal escape of LNPs [ 109 ].…”

Section: Strategy To Achieve Efficient Sirna Deliverymentioning

confidence: 99%

Recent advances in siRNA delivery mediated by lipid-based nanoparticles

Yonezawa

Koide

Asai

2020

Advanced Drug Delivery Reviews

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258

157

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Small interfering RNA (siRNA) has been expected to be a unique pharmaceutic for the treatment of broad-spectrum intractable diseases. However, its unfavorable properties such as easy degradation in the blood and negative-charge density are still a formidable barrier for clinical use. For disruption of this barrier, siRNA delivery technology has been significantly advanced in the past two decades. The approval of Patisiran (ONPATTRO™) for the treatment of transthyretin-mediated amyloidosis, the first approved siRNA drug, is a most important milestone. Since lipid-based nanoparticles (LNPs) are used in Patisiran, LNP-based siRNA delivery is now of significant interest for the development of the next siRNA formulation. In this review, we describe the design of LNPs for the improvement of siRNA properties, bioavailability, and pharmacokinetics. Recently, a number of siRNA-encapsulated LNPs were reported for the treatment of intractable diseases such as cancer, viral infection, inflammatory neurological disorder, and genetic diseases. We believe that these contributions address and will promote the development of an effective LNP-based siRNA delivery system and siRNA formulation.

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Key determinants of siRNA delivery mediated by unique pH-responsive lipid-based liposomes

Cited by 15 publications

References 31 publications

The Dual Role of Macropinocytosis in Cancers: Promoting Growth and Inducing Methuosis to Participate in Anticancer Therapies as Targets

The Dual Role of Macropinocytosis in Cancers: Promoting Growth and Inducing Methuosis to Participate in Anticancer Therapies as Targets

Rationale and Application of PEGylated Lipid-Based System for Advanced Target Delivery of siRNA

Recent advances in siRNA delivery mediated by lipid-based nanoparticles

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