Non-viral nanoparticles for RNA interference: Principles of design and practical guidelines

Liu, Zehua; Wang, Shiqi; Tapeinos, Christos; Känkänen, Voitto; El‐Sayed, Nesma; Python, André; Hirvonen, Jouni; Santos, Hélder A.

doi:10.1016/j.addr.2021.05.018

Cited by 43 publications

(31 citation statements)

References 333 publications

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“…The endosomal/lysosomal escape behaviors of nanocarriers containing cationic lipids such as DOTAP, cationic polymers such as PEI and PAMAM, and calcium phosphates can be explained by “proton sponge effect”, which usually have ionizable amine groups and strong buffering capacities in the pH range of 5 to 7. However, the exact mechanism of “proton sponge effect” is still being debated [ 181 ]. Besides “proton sponge effect”, Vesicles containing gas that can release gas in acidic lumen triggered by ultrasound, laser or acid are proposed to break the endosomal compartments as well through membrane rupture [ 182 ].…”

Section: Synthetic Non-viral Vectors For Rna Deliverymentioning

confidence: 99%

Non-viral vectors for RNA delivery

Yan

Liu

et al. 2022

Journal of Controlled Release

157

100

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RNA-based therapy is a promising and potential strategy for disease treatment by introducing exogenous nucleic acids such as messenger RNA (mRNA), small interfering RNA (siRNA), microRNA (miRNA) or antisense oligonucleotides (ASO) to modulate gene expression in specific cells. It is exciting that mRNA encoding the spike protein of COVID-19 (coronavirus disease 2019) delivered by lipid nanoparticles (LNPs) exhibits the efficient protection of lungs infection against the virus. In this review, we introduce the biological barriers to RNA delivery in vivo and discuss recent advances in non-viral delivery systems, such as lipid-based nanoparticles, polymeric nanoparticles, N -acetylgalactosamine (GalNAc)-siRNA conjugate, and biomimetic nanovectors, which can protect RNAs against degradation by ribonucleases, accumulate in specific tissue, facilitate cell internalization, and allow for the controlled release of the encapsulated therapeutics.

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Section: Synthetic Non-viral Vectors For Rna Deliverymentioning

confidence: 99%

Non-viral vectors for RNA delivery

Yan

Liu

et al. 2022

Journal of Controlled Release

157

100

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“…A new oncology tool, RNA interference (RNAi) therapy, has made significant progress in gene therapy due to its properties that can improve the poor prognosis of cancer patients. [ 145 ] RNA interference therapeutics, comprising small interfering RNA (siRNA) and microRNA (miRNA), achieve therapeutic effects by silencing genes. [ 146 ] Currently, the ability of vectors such as PAMAM dendrimers to deliver RNA to tumor cells has been well established.…”

Section: Utilization Of Dendrimers In Cancermentioning

confidence: 99%

Polymeric Dendrimers as Nanocarrier Vectors for Neurotheranostics

Zha

Liu

et al. 2022

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immune responses, activating cellular machinery causing cell stress, cytotoxicity, lack of selectivity, increasing the likelihood of replication competence, and the constrained structure of insert-size, which can limit their biological and medical applications. [2][3][4] By contrast, various forms of nonviral vectors are widely developed and applied in biomedical research because of their low immunogenicity, high biocompatibility, simplicity in structural pattern, ease of size adjustment, practicality in designing various active sites, and low cost of production. [5,6] The most widely studied nonviral vectors are liposomes, inorganic nanoparticles, polymers, and dendrimers. [7] Liposomes are small spherical vesicles from cholesterol and phospholipids characterized with the surface that can be modified using glycolipids or sialic acid. Yet, the unmodified forms of liposomes are structurally unstable and could easily be eliminated by means of body circulation. [8] In this situation, stable inorganic nanoparticles, such as calcium phosphate (Ca 3 (PO 4 ) 2 ), gold (Au), iron oxide (Fe 3 O 4 ), and lanthanide-based nanoparticles are widely used, mainly due to their good hydrophilicity and excellent biocompatibility. [9][10][11] Depending on their chemical core composition, these inorganic nanoparticles display different properties and efficiencies. Lately, inorganic nanoparticles have been developed as effective drug delivery systems and used in many diagnostic techniques. [12] In addition, polymers are widely used as nonviral vectors as well. [13][14][15] Polymers are biodegradable nanomaterials with stable and easily modifiable 3D structures. Their uncomplicated synthesis process allows for large-scale production and safe clinical use compared to inorganic nanoparticles. [16] Notably, dendrimers are hyperbranched polymers with a well-defined chemical structure: a core at the center occupied by array of convergent reactive chain-ends and surface that can easily be modified. [17] The chemistry of dendrimers was first described by Buhleier et al. in 1978. [18] In 1985, Tomalia et al. reported a newer kind of dendrimers based on the mixture of amines and amides, termed polyamidoamine (PAMAM) dendrimers. [19] Dendrimers are intermeshed synthetic organic macromolecules with 3D architecture composition and abundant terminal functional groups. They are well-defined monodispersity-sized materials with extraordinary membrane interaction properties Dendrimers are polymers with well-defined 3D branched structures that are vastly utilized in various neurotheranostics and biomedical applications, particularly as nanocarrier vectors. Imaging agents can be loaded into dendrimers to improve the accuracy of diagnostic imaging processes. Likewise, combining pharmaceutical agents and anticancer drugs with dendrimers can enhance their solubility, biocompatibility, and efficiency. Practically, by modifying ligands on the surface of dendrimers, effective therapeutic and diagnostic platforms can be constructed and implemented for target...

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“…Along with the antiviral properties, NPs offer a stable delivery system for unstable therapeutics such as microRNAs (miR, miRNA) that are otherwise unstable. Furthermore, concerning their potential advantages, including refined safety, high delivery capability, and economic viability, NPs have been substantially considered to act as RNA molecule carriers [101] . Cerium oxide nanoparticles (CNP) are promising nanocarrier molecules considering local treatment.…”

Section: Introductionmentioning

confidence: 99%