RGD Conjugated Dendritic Polylysine for Cellular Delivery of Antisense Oligonucleotide

Le, Thanh-Do; Nakagawa, Osamu; Fisher, Martin; Juliano, R. L.; Yoo, Hah Young

doi:10.1166/jnn.2017.13335

Cited by 10 publications

(5 citation statements)

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“…To improve cellular uptake, asONs are conjugated with various delivery-promoting molecules, including cholesterol [ 36 ], polyethylene glycol [ 37 , 38 ], α-tocopherol [ 39 , 40 ], cell-penetrating peptides [ 41 , 42 ], etc. Despite the perspective of this approach, the redundant modifications of asONs with such molecules, especially in combination with modifications of the oligonucleotide backbone to improve their nuclease resistance, can significantly affect their biological activity, create problems in adaptation of length and composition of linker groups and, finally, complicate the scheme of asON synthesis and isolation as well as increase their cost.…”

Section: Introductionmentioning

confidence: 99%

Transport Oligonucleotides—A Novel System for Intracellular Delivery of Antisense Therapeutics

et al. 2020

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Biological activity of antisense oligonucleotides (asON), especially those with a neutral backbone, is often attenuated by poor cellular accumulation. In the present proof-of-concept study, we propose a novel delivery system for asONs which implies the delivery of modified antisense oligonucleotides by so-called transport oligonucleotides (tON), which are oligodeoxyribonucleotides complementary to asON conjugated with hydrophobic dodecyl moieties. Two types of tONs, bearing at the 5′-end up to three dodecyl residues attached through non-nucleotide inserts (TD series) or anchored directly to internucleotidic phosphate (TP series), were synthesized. tONs with three dodecyl residues efficiently delivered asON to cells without any signs of cytotoxicity and provided a transfection efficacy comparable to that achieved using Lipofectamine 2000. We found that, in the case of tON with three dodecyl residues, some tON/asON duplexes were excreted from the cells within extracellular vesicles at late stages of transfection. We confirmed the high efficacy of the novel and demonstrated that MDR1 mRNA targeted asON delivered by tON with three dodecyl residues significantly reduced the level of P-glycoprotein and increased the sensitivity of KB-8-5 human carcinoma cells to vinblastine. The obtained results demonstrate the efficacy of lipophilic oligonucleotide carriers and shows they are potentially capable of intracellular delivery of any kind of antisense oligonucleotides.

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Section: Introductionmentioning

confidence: 99%

Transport Oligonucleotides—A Novel System for Intracellular Delivery of Antisense Therapeutics

et al. 2020

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“…The results were attributed to the specific binding ability of iRGD to integrin receptors αvβ3 and αvβ5 overexpressed in tumour cells [ 30 , 31 ]. Upon cleavage by proteases, the C-terminal rule (C and R) motif is exposed and consequently binds to the neurexin-1 (NRP-1) receptor; the cleaved form of iRGD binds to NRP-1 and subsequently triggers NRP-1-dependent endocytosis, thereby enhancing tumour penetration [ 32 ].…”

Section: Resultsmentioning

confidence: 99%

The Antitumour Activity of a Curcumin and Piperine Loaded iRGD-Modified Liposome: In Vitro and In Vivo Evaluation

Wang,

Huang,

Chen

et al. 2023

Molecules

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Lung cancer is one of the most common cancers around the world, with a high mortality rate. Despite substantial advancements in diagnoses and therapies, the outlook and survival of patients with lung cancer remains dismal due to drug tolerance and malignant reactions. New interventional treatments urgently need to be explored if natural compounds are to be used to reduce toxicity and adverse effects to meet the needs of lung cancer clinical treatment. An internalizing arginine-glycine-aspartic acid (iRGD) modified by a tumour-piercing peptide liposome (iRGD-LP-CUR-PIP) was developed via co-delivery of curcumin (CUR) and piperine (PIP). Its antitumour efficacy was evaluated and validated via in vivo and in vitro experiments. iRGD-LP-CUR-PIP enhanced tumour targeting and cellular internalisation effectively. In vitro, iRGD-LP-CUR-PIP exhibited enhanced cellular uptake, suppression of tumour cell multiplication and invasion and energy-independent cellular uptake. In vivo, iRGD-LP-CUR-PIP showed high antitumour efficacy, mainly in terms of significant tumour volume reduction and increased weight and spleen index. Data showed that iRGD peptide has active tumour targeting and it significantly improves the penetration and cellular internalisation of tumours in the liposomal system. The use of CUR in combination with PIP can exert synergistic antitumour activity. This study provides a targeted therapeutic system based on natural components to improve antitumour efficacy in lung cancer.

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“…The specificity of the RGD peptide depends on the backbone conformation, the charged side chains of the Arg and Asp residues, and the hydrophobic moieties of the flanks of Asp residues (Schaffner and Dard 2003). The RGD motif's freedom of conformation determines its binding strength to the integrin, and molecular dynamics simulations have shown that while RGD motifs are mostly exposed to solvents that can be bound in all synthetic systems, their flexibility depends on the refined geometry (Le et al 2017). The interaction between the RGD peptides and integrin αVβ3 is influenced by direction and distance (Dong et al 2017).…”

Section: Structure Of Rgdmentioning

confidence: 99%

Recent Research Progress of RGD Peptide–Modified Nanodrug Delivery Systems in Tumor Therapy

Li-yan

Wang

et al. 2023

Int J Pept Res Ther

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There have been great advancements in targeted nanodrug delivery systems for tumor therapy. Liposomes, polymeric nanoparticles, and inorganic nanoparticles are commonly employed as nanocarriers for drug delivery, and it has been found that arginine glycine aspartic acid (RGD) peptides and their derivatives can be used as ligands of integrin receptors to enhance the direct targeting ability. In this paper, we review the recent applications of RGD-modified liposomes, polymeric nanoparticles, and inorganic nanocarriers in cancer diagnosis and treatment, discuss the current challenges and prospects, and examine the progress made by the latest research on RGD peptide–modified nano delivery systems in cancer therapy. In recent years, RGD peptide–modified nanodrug delivery systems have been proven to have great potential in tumor therapy. Finally, we provide an overview of the current limitations and future directions of RGD peptide–modified nano-drug delivery systems for cancer therapy. This review aims to elucidate the contribution of RGD peptide–modified nanodrug delivery systems in the field of tumor therapy.

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RGD Conjugated Dendritic Polylysine for Cellular Delivery of Antisense Oligonucleotide

Cited by 10 publications

References 0 publications

Transport Oligonucleotides—A Novel System for Intracellular Delivery of Antisense Therapeutics

Transport Oligonucleotides—A Novel System for Intracellular Delivery of Antisense Therapeutics

The Antitumour Activity of a Curcumin and Piperine Loaded iRGD-Modified Liposome: In Vitro and In Vivo Evaluation

Recent Research Progress of RGD Peptide–Modified Nanodrug Delivery Systems in Tumor Therapy

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