Journal
ACS APPLIED BIO MATERIALS
Volume 4, Issue 2, Pages 1783-1793Publisher
AMER CHEMICAL SOC
DOI: 10.1021/acsabm.0c01519
Keywords
microfluidics; lipid nanoparticles; noncationic lipids; siRNA delivery; nanomedicines; exosomes-like nanoparticles
Funding
- JST, CREST, Japan [JPMJCR17H1]
- JST, PRESTO, Japan [JPMJPR19K8]
- Special Education and Research Expenses from the Ministry of Education, Culture, Sports, Science and Technology
- JSPS KAKENHI [JP19J20939, JP19KK0140]
- 2020 Feasibility Study Program of the Frontier Chemistry Center, Faculty of Engineering, Hokkaido University
- Hosokawa Powder Technology Foundation
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Size-controlled lipid nanoparticles (LNPs) are a leading technology for gene therapies that use DNA/RNA delivery. The use of cationic lipids for encapsulating DNA/RNA into LNPs can lead to cytotoxicity, prompting the exploration of noncationic nanocarriers like exosomes for more ideal delivery. The development of a simple one-step method for producing size-controlled noncationic NPs encapsulating DNA/RNA remains challenging, but a microfluidic-based approach shows promise in efficiently encapsulating siRNA into customizable NPs for gene therapy applications.
Size-controlled lipid nanoparticle (LNP)-based DNA/RNA delivery is a leading technology for gene therapies. For DNA/RNA delivery, typically, a cationic lipid is used to encapsulate DNA/RNA into LNPs. However, the use of the cationic lipid leads to cytotoxicity. In contrast, noncationic NPs, such as exosomes, are ideal nanocarriers for DNA/RNA delivery. However, the development of a simple one-step method for the production of size-controlled noncationic NPs encapsulating DNA/RNA is still challenging because of the lack of electrostatic interactions between the cationic lipid and negatively charged DNA/RNA. Herein, we report a microfluidic-based one-step method for the production of size-controlled noncationic NPs encapsulating small interfering RNA (siRNA). Our microfluidic device, named iLiNP, enables the efficient encapsulation of siRNA, as well as control over the NP size, by varying the flow conditions. We applied this method to produce size-controlled exosome-like NPs. The siRNA-loaded exosome-like NPs did not show in vitro cytotoxicity at a high siRNA dosage. In addition, we investigated the effect of the size of the exosome-like NPs on the target gene silencing and found that the 40-50 nm-sized NPs suppressed target protein expression at a dose of 20 nM siRNA. The iLiNP-based one-step production method for size-controlled noncationic-NP-encapsulated RNA is a promising method for the production of artificial exosomes and functionally modified exosomes for gene and cell therapies.
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