Enhancing the Therapeutic Delivery of Oligonucleotides by Chemical Modification and Nanoparticle Encapsulation

Sun, Yating; Zhao, Yarong; Zhao, Xiuting; Lee, Robert J.; Teng, Lirong; Zhou, Chenguang

doi:10.3390/molecules22101724

Cited by 44 publications

(43 citation statements)

References 104 publications

(134 reference statements)

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“…Besides these drugs, there are still a large number of oligonucleotide drug candidates being widely evaluated in clinical studies [ 6 , 7 ]. The common pharmacological challenges for single-strand oligonucleotides are their susceptibility to nuclease degradation, and massive dose requirement [ 1 , 8 ]. During the past years, chemical modification and structural optimization on single-strand oligonucleotides have been proposed to overcome these limitations, i.e., the phosphate backbone of oligonucleotides was replaced by phosphorothioate, phosphodiamine morpholino, and peptide backbones [ 9 – 11 ].…”

Section: Introductionmentioning

confidence: 99%

Natural polyphenol assisted delivery of single-strand oligonucleotides by cationic polymers

et al. 2020

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Single-strand oligonucleotides provide promising potential as new therapeutics towards various diseases. However, the efficient delivery of oligonucleotide therapeutics is still challenging due to their susceptibility to nuclease degradation and the lack of effective carriers for condensation. In this study, we reported the use of natural polyphenol to facilitate the condensation of single-strand oligonucleotides by cationic polymers. Green tea catechin complexed with single-strand oligonucleotides to form anionic nanoparticles, which were further coated by low molecular weight cationic polymers to increase their cell internalization. The resulting core-shell structured nanoparticles, so-called green nanoparticles (GNPs), showed improved cargo stability, and achieved high efficiency in the delivery of several types of single-strand oligonucleotides including antisense oligonucleotides, anti-miRNA, and DNAzyme. This study provides a facile strategy for the efficient delivery of single-strand oligonucleotides.

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Section: Introductionmentioning

confidence: 99%

Natural polyphenol assisted delivery of single-strand oligonucleotides by cationic polymers

et al. 2020

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“…The opsonization process makes siRNA carriers more susceptible to RES filtration and results in fast renal clearance ( Figure 4 ) [ 55 ]. Opsonized carriers loaded RNA drugs accumulate in the liver and spleen and may cause toxic effects [ 105 ]. Thus, ultimately opsonization process reduces the therapeutic concentration needed for their efficient RNAi activity [ 55 ].…”

Section: Protein Bindingmentioning

confidence: 99%

“…Surface modifications are the primary strategies to reduce the interaction between opsonin proteins adsorption and RNAi carriers. Coating of positively charge carriers with hydrophilic polymers such as PEG or specific synthetic polymers significantly decreases the opsonization along with unspecific binding [ 105 , 106 ]. For example, palmitate-avidin containing PLGA carrier adsorbed PEG-biotin on their surface, and the 10 kDa PEG-coated particle reduced protein adsorption by 75% [ 107 ].…”

Section: Protein Bindingmentioning

confidence: 99%

Overcoming Barriers for siRNA Therapeutics: From Bench to Bedside

et al. 2020

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The RNA interference (RNAi) pathway possesses immense potential in silencing any gene in human cells. Small interfering RNA (siRNA) can efficiently trigger RNAi silencing of specific genes. FDA Approval of siRNA therapeutics in recent years garnered a new hope in siRNA therapeutics. However, their therapeutic use is limited by several challenges. siRNAs, being negatively charged, are membrane-impermeable and highly unstable in the systemic circulation. In this review, we have comprehensively discussed the extracellular barriers, including enzymatic degradation of siRNAs by serum endonucleases and RNAases, rapid renal clearance, membrane impermeability, and activation of the immune system. Besides, we have thoroughly described the intracellular barriers such as endosomal trap and off-target effects of siRNAs. Moreover, we have reported most of the strategies and techniques in overcoming these barriers, followed by critical comments in translating these molecules from bench to bedside.

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“…One of the biggest challenges is to ensure the delivery efficiency of miRNAs mimics to target cells. While RNase is abundant in serum and cytoplasm, miRNAs is short-lived in plasma (Sun et al, 2017). Moreover, chemically modify nucleotides can increase miRNAs expression and stability, but they are limited due to the low membrane penetrability.…”

Section: Mirna Lncrna-based Therapeutics In C-met-related Cancermentioning

confidence: 99%

MicroRNAs and Long Non-coding RNAs in c-Met-Regulated Cancers

Zhan

Zhang

et al. 2020

Front. Cell Dev. Biol.

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MicroRNAs (miRNAs) and long non-coding RNAs (lncRNAs) are components of many signaling pathways associated with tumor aggressiveness and cancer metastasis. Some lncRNAs are classified as competitive endogenous RNAs (ceRNAs) that bind to specific miRNAs to prevent interaction with target mRNAs. Studies have shown that the hepatocyte growth factor/mesenchymal-epithelial transition factor (HGF/c-Met) pathway is involved in physiological and pathological processes such as cell growth, angiogenesis, and embryogenesis. Overexpression of c-Met can lead to sustained activation of downstream signals, resulting in carcinogenesis, metastasis, and resistance to targeted therapies. In this review, we evaluated the effects of anti-oncogenic and oncogenic non-coding RNAs (ncRNAs) on c-Met, and the interactions among lncRNAs, miRNAs, and c-Met in cancer using clinical and tissue chromatin immunoprecipition (ChIP) analysis data. We summarized current knowledge of the mechanisms and effects of the lncRNAs/miR-34a/c-Met axis in various tumor types, and evaluated the potential therapeutic value of lncRNAs and/or miRNAs targeted to c-Met on drug-resistance. Furthermore, we discussed the functions of lncRNAs and miRNAs in c-Met-related carcinogenesis and potential therapeutic strategies.

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Enhancing the Therapeutic Delivery of Oligonucleotides by Chemical Modification and Nanoparticle Encapsulation

Cited by 44 publications

References 104 publications

Natural polyphenol assisted delivery of single-strand oligonucleotides by cationic polymers

Natural polyphenol assisted delivery of single-strand oligonucleotides by cationic polymers

Overcoming Barriers for siRNA Therapeutics: From Bench to Bedside

MicroRNAs and Long Non-coding RNAs in c-Met-Regulated Cancers

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