New Applications of Lipid and Polymer-Based Nanoparticles for Nucleic Acids Delivery

Niculescu, Adelina-Gabriela; Bîrcă, Alexandra Cătălina; Grumezescu, Alexandru Mihai

doi:10.3390/pharmaceutics13122053

Cited by 25 publications

(9 citation statements)

References 114 publications

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“…However, it needs to be mentioned that the manufacturer’s structures for Lipofectamine do recommend removing serum from the media while exposing the cells to this transfection agent. Rapid enzymatic degradation is one of the major challenges in efficient nucleic acid delivery . This vulnerability is one of the drawbacks of the siRNA conjugates.…”

Section: Resultsmentioning

confidence: 99%

“…Rapid enzymatic degradation is one of the major challenges in efficient nucleic acid delivery. 46 This vulnerability is one of the drawbacks of the siRNA conjugates. For example, it has been shown that phosphothioethanol conjugated siRNA can only extend the degradation time from 0.5 to 6 h. 47 A higher level of protection is usually expected from "encapsulation" approaches that limit the access to siRNA and have been reported to protect siRNA for up to 24 h in the presence of serum.…”

Section: Serum Stability Of the Peptide/sirna Complexmentioning

confidence: 99%

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Redox-Responsive Disulfide Cyclic Peptides: A New Strategy for siRNA Delivery

et al. 2022

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RNA interference (RNAi) is a powerful tool capable of targeting virtually any protein without time-consuming and expensive drug development studies. However, due to obstacles facing efficient and safe delivery, RNAi-based therapeutic approach remains a challenge. Herein, we have designed and synthesized a number of disulfide-constraining cyclic and hybrid peptides using tryptophan and arginine residues. Our hypothesis was that peptide structures would undergo reduction by intracellular glutathione (more abundant in cancer cells) and unpack the small interfering RNA (siRNA) from the peptide/siRNA complexes. A subset of newly developed peptides (specifically, C4 and H4) exhibited effective cellular internalization of siRNA (∼70% of the cell population; monitored by flow cytometry and confocal microscopy), the capability of protecting siRNA against early degradation by nucleases (monitored by gel electrophoresis), minimal cytotoxicity in selected cell lines (studied by cell viability and LC50 calculations), and efficient protein silencing by 70–75% reduction in the expression of targeting signal transducer and activator of transcription 3 (STAT3) in human triple-negative breast cancer (TNBC) MDA-MB-231 cells, analyzed using the Western blot technique. Our results indicate the birth of a promising new family of siRNA delivery systems that are capable of safe and efficient delivery, even in the presence of nucleases.

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Section: Resultsmentioning

confidence: 99%

Section: Serum Stability Of the Peptide/sirna Complexmentioning

confidence: 99%

Redox-Responsive Disulfide Cyclic Peptides: A New Strategy for siRNA Delivery

et al. 2022

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“…Despite being recognized for a long time, endosomal escape remains one of the unresolved bottlenecks in the way of effective LNP design [136]. Following the cellular entry, LNPs will be trapped in endosomes, from which only a small fraction may be able to successfully escape.…”

Section: Endosomal Escapementioning

confidence: 99%

siRNA Functionalized Lipid Nanoparticles (LNPs) in Management of Diseases

et al. 2022

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RNAi (RNA interference)-based technology is emerging as a versatile tool which has been widely utilized in the treatment of various diseases. siRNA can alter gene expression by binding to the target mRNA and thereby inhibiting its translation. This remarkable potential of siRNA makes it a useful candidate, and it has been successively used in the treatment of diseases, including cancer. However, certain properties of siRNA such as its large size and susceptibility to degradation by RNases are major drawbacks of using this technology at the broader scale. To overcome these challenges, there is a requirement for versatile tools for safe and efficient delivery of siRNA to its target site. Lipid nanoparticles (LNPs) have been extensively explored to this end, and this paper reviews different types of LNPs, namely liposomes, solid lipid NPs, nanostructured lipid carriers, and nanoemulsions, to highlight this delivery mode. The materials and methods of preparation of the LNPs have been described here, and pertinent physicochemical properties such as particle size, surface charge, surface modifications, and PEGylation in enhancing the delivery performance (stability and specificity) have been summarized. We have discussed in detail various challenges facing LNPs and various strategies to overcome biological barriers to undertake the safe delivery of siRNA to a target site. We additionally highlighted representative therapeutic applications of LNP formulations with siRNA that may offer unique therapeutic benefits in such wide areas as acute myeloid leukaemia, breast cancer, liver disease, hepatitis B and COVID-19 as recent examples.

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“…To overcome these limitations, different nonviral delivery systems, such as cationic polymers, lipids, inorganic nanoparticles, and dendrimers, have been developed. − These formulations showed varying levels of success in delivering nucleic acids into cells. ,, An alternative approach of polymer–lipid hybrid nanoparticles has been investigated for nucleic acid delivery due to their attractive properties of biocompatibility, biodegradability, and ease of synthesis. Previous studies showed that polymer–lipid nanoparticles efficiently deliver drugs, mRNA, plasmid DNA, and siRNA into cells. − Hybrid nanoparticles protect nucleic acids from degradation by nucleases. , They can interact with the cell membrane and internalize into cells by endocytosis. Recent studies showed that polymer–lipid nanoparticles promote nucleic acid escape from the endolysosomal compartments and increase gene silencing efficiency. − Then, the conjugated nucleic acids are released from the carrier system in the cytosol, where RNAi is initiated .…”

Section: Introductionmentioning

confidence: 99%

Protamine–Lipid–dsRNA Nanoparticles Improve RNAi Efficiency in the Fall Armyworm, Spodoptera frugiperda

Dhandapani

Gurusamy

Palli

2022

J. Agric. Food Chem.

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Developing safe and effective double-stranded RNA (dsRNA) delivery systems remains a major challenge for gene silencing, especially in lepidopteran insects. This study evaluated the protamine sulfate (PS)/lipid/dsRNA nanoparticle (NP) delivery system for RNA interference (RNAi) in cells and larvae of the fall armyworm (FAW), Spodoptera frugiperda, a major worldwide pest. A highly efficient gene delivery formulation was prepared using a cationic biopolymer, PS, and a cationic lipid, Cellfectin (CF), complexed with dsRNA. The NPs were prepared by a two-step self-assembly method. The formation of NPs was revealed by dynamic light scattering and transmission electron microscopy. The formation of CF/dsRNA/PS NPs was spherical in shape and size, ranging from 20 to 100 nm with a positive charge (+23.3 mV). Interestingly, prepared CF/dsRNA/PS NPs could protect dsRNA (95%) from nuclease degradation and thus significantly improve the stability of dsRNA. Formulations prepared by combining EGFP DNA with CF/PS increased transfection efficiency in Sf9 cells compared to PS/EGFP and CF/EGFP NPs. Also, the PS/CF/dsRNA NPs enhanced the endosomal escape for the intracellular delivery of dsRNA. The gene knockdown efficiency was assessed in Sf9 Luciferase (Luc) stable cells after a 72 h incubation with CF/dsRNA/PS, PS/dsRNA, CF/dsRNA, or naked dsRNA. Knockdown of the Luc gene was detected in CF/dsRNA/PS (76%) and PS/dsRNA (42.4%) not CF/dsRNA (19.5%) and naked dsRNA (10.3%) in Sf9 Luc cells. Moreover, CF/dsIAP/PS (25 μg of dsRNA targeting the inhibitor of apoptosis, IAP, gene of FAW) NPs showed knockdown of the IAP gene (39.5%) and mortality (55%) in FAW larvae. These results highlight the potential application of PS/lipid/dsRNA NPs for RNA-mediated control of insect pests.

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New Applications of Lipid and Polymer-Based Nanoparticles for Nucleic Acids Delivery

Cited by 25 publications

References 114 publications

Redox-Responsive Disulfide Cyclic Peptides: A New Strategy for siRNA Delivery

Redox-Responsive Disulfide Cyclic Peptides: A New Strategy for siRNA Delivery

siRNA Functionalized Lipid Nanoparticles (LNPs) in Management of Diseases

Protamine–Lipid–dsRNA Nanoparticles Improve RNAi Efficiency in the Fall Armyworm, Spodoptera frugiperda

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