Cell-Penetrating Peptides Delivering siRNAs: An Overview

Falato, Luca; Gestin, Maxime; Langel, Ülo

doi:10.1007/978-1-0716-1298-9_18

Cited by 35 publications

(18 citation statements)

References 152 publications

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“…Especially in cancer research, CPPs are a significant therapeutic delivery tool [ 16 – 18 ]. By CCPs delivery, proteins, plasmids, siRNA, nanoparticles, PNAs, and liposomes, which are not able to enter cells alone have been transported into the cells [ 4 , 19 – 21 ]. CPPs are classified into three categories according to their physicochemical properties: cationic, amphiphilic, and hydrophobic.…”

Section: Discussionmentioning

confidence: 99%

BR2 cell penetrating peptide effectively delivers anti-p21Ras scFv to tumor cells with ganglioside expression for therapy of ras-driven tumor

Takata

Shi

Pan³

et al. 2022

PLoS ONE

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Purpose Cell membrane penetrating peptide BR2 can bind with ganglioside and introduce foreign drugs into tumor cells. In this study, we employed BR2 to carry the broad-spectrum anti-p21Ras scFv prepared in our laboratory into ganglioside expressing tumor cells for therapy of ras-driven tumors. Methods BR2-p21Ras scFv gene was cloned to prokaryotic expression vector and expressed in E. coli BL21, then the fusion protein was purified with HisPur Ni-NTA. The immunoreactivity of the fusion protein with p21Ras was detected by ELISA and western blotting. The membrane-penetrating and immune co-localization with p21Ras of the fusion protein were determined by immunofluorescence. The antitumor activity was investigated using MTT, wound healing, colone formation, and apoptosis assays in vitro. Results BR2-p21Ras scFv fusion protein was successfully expressed and purified. We found that the fusion protein could specifically penetrate into human tumor cell lines which express ganglioside including human neuroblastoma cell line SK-N-SH, human colon cancer cell line HCT116 and human glioma cell line U251. After entering tumor cells the fusion protein bonded specifically with p21Ras. In vitro experiments revealed that it could significantly inhibit the proliferation, migration, and colone formation of HCT116, SK-N-SH, and U251 cells and promote the apoptosis of these tumor cells. Conclusions BR2-p21Ras scFv can penetrate ganglioside expressing tumor cells and inhibit the growth of ras-driven tumor by binding with p21Ras, and producing an inhibitory effect. It is suggested that BR2-p21Ras scFv is a potential ras-driven tumor therapeutic antibody.

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Section: Discussionmentioning

confidence: 99%

BR2 cell penetrating peptide effectively delivers anti-p21Ras scFv to tumor cells with ganglioside expression for therapy of ras-driven tumor

Takata

Shi

Pan³

et al. 2022

PLoS ONE

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“…This strategy also provides greater efficiency for lung cancer, which is regularly associated with considerable adverse effects in healthy tissues [69]. Small interfering RNAs (siRNAs) are double-stranded RNA molecules that silence the expression of a specific protein through the RNA interference pathway [72]. siRNAs have emerged as anticancer therapeutics and have been widely used in recent studies [73,74].…”

Section: Ph-responsivementioning

confidence: 99%

Smart Nanotherapeutics and Lung Cancer

et al. 2021

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Lung cancer is a significant health problem worldwide. Unfortunately, current therapeutic strategies lack a sufficient level of specificity and can harm adjacent healthy cells. Consequently, to address the clinical need, novel approaches to improve treatment efficiency with minimal side effects are required. Nanotechnology can substantially contribute to the generation of differentiated products and improve patient outcomes. Evidence from previous research suggests that nanotechnology-based drug delivery systems could provide a promising platform for the targeted delivery of traditional chemotherapeutic drugs and novel small molecule therapeutic agents to treat lung cancer cells more effectively. This has also been found to improve the therapeutic index and reduce the required drug dose. Nanodrug delivery systems also provide precise control over drug release, resulting in reduced toxic side effects, controlled biodistribution, and accelerated effects or responses. This review highlights the most advanced and novel nanotechnology-based strategies, including targeted nanodrug delivery systems, stimuli-responsive nanoparticles, and bio-nanocarriers, which have recently been employed in preclinical and clinical investigations to overcome the current challenges in lung cancer treatments.

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“…Cell-penetrating peptides (CPPs, also known as protein transduction domains) are short peptides (typically 10 to 30 amino acids) capable of enhancing the cellular internalisation of either covalently conjugated or co-delivered cargos, including mAb-based imaging and therapeutic agents, 5–7 mostly by energy-dependant endocytosis mechanisms. 8,9 Notably, the TAT peptide (GRKKRRQRRRPPQGYG) derived from the transactivator of transcription protein of the HIV-1 virus has been widely applied as a CPP, including in the development of antibody–CPP conjugates which have emerged in recent years.…”

Section: Introductionmentioning

confidence: 99%

“…However, this otherwise attractive imaging modality is similarly limited by inefficient internalisation and endosomal entrapment of mAb-derived probes which restricts the scope of this application to a small subset of clinically relevant cell surface biomarkers, in contrast to the rich pool of biomarkers located inside cells. [2][3][4] Cell-penetrating peptides (CPPs, also known as protein transduction domains) are short peptides (typically 10 to 30 amino acids) capable of enhancing the cellular internalisation of either covalently conjugated or co-delivered cargos, including mAb-based imaging and therapeutic agents, [5][6][7] mostly by energy-dependant endocytosis mechanisms. 8,9 Notably, the TAT peptide (GRKKRRQRRRPPQGYG) derived from the transactivator of transcription protein of the HIV-1 virus has been widely applied as a CPP, including in the development of antibody-CPP conjugates which have emerged in recent years.…”

Section: Introductionmentioning

confidence: 99%