RIPL peptide (IPLVVPLRRRRRRRRC)-conjugated liposomes for enhanced intracellular drug delivery to hepsin-expressing cancer cells

Kang, Min Gyu; Park, Min Jung; Yoo, Hyun Joon; hyuk, Kwon Yie; Lee, Sang Gon; Kim, Dae Jung; Yeom, Dong Woo; Kang, Myung Joo; Choi, Young Wook

doi:10.1016/j.ejpb.2014.03.016

Cited by 35 publications

(41 citation statements)

References 50 publications

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“…Newer systems, based on dynamic as well as electrophoretic and static light scattering in combination, seem to allow quantitative analysis of EVs of several microns in diameter. However, their application has been limited to the use of liposomes in drug delivery experiments[146]. …”

Section: Ev Isolation and Detection Methodsmentioning

confidence: 99%

Extracellular Vesicles in Cancer: Exosomes, Microvesicles and the Emerging Role of Large Oncosomes

Minciacchi

Freeman

Vizio

2015

Seminars in Cell & Developmental Biology

773

638

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Since their first description, extracellular vesicles (EVs) have been the topic of avid study in a variety of physiologic contexts and are now thought to play an important role in cancer. The state of knowledge on biogenesis, molecular content and horizontal communication of diverse types of cancer EVs has expanded considerably in recent years. As a consequence, a plethora of information about EV composition and molecular pathways involved in the regulation of important biological processes has emerged, along with the notion that cancer cells rely on these particles to invade tissues and propagate oncogenic signals at distance. In vivo studies, designed to achieve a deeper understanding of the extent to which EV biology can be applied to clinically relevant settings, are increasing. This review will summarize recent studies on EVs functionally implicated in cancer, with a focus on a novel EV population referred to as large oncosomes, which originate from highly migratory, amoeboid tumor cells. Here we provide an overview about the biogenesis and composition of exosomes, microvesicles and large oncosomes, along with their cancer-specific and more general functions. We also discuss current challenges and emerging technologies that might improve EV detection in various systems. Further studies on the functional role of EVs in specific steps of cancer formation and progression will expand our understanding of the diversity of paracrine signaling mechanisms in malignant growth.

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Section: Ev Isolation and Detection Methodsmentioning

confidence: 99%

Extracellular Vesicles in Cancer: Exosomes, Microvesicles and the Emerging Role of Large Oncosomes

Minciacchi

Freeman

Vizio

2015

Seminars in Cell & Developmental Biology

773

638

View full text Add to dashboard Cite

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“…They have been explored in a wide variety of theranostic applications in cancer, including the intracellular delivery of small anticancer drugs, macromolecules and nanoparticle systems [27][28][29]. Cationic peptides which are rich in arginine residues were employed as CPPs such as TAT peptide (TATp), penetratin, low molecular weight protamine (LMWP) and oligoarginines [3,30,31]. Octa-arginine (R8), a short chain peptide having eight arginine residues was investigated by many researchers and proved to be efficient in transporting a variety of cargoes into the cells [32][33][34].…”

Section: Introductionmentioning

confidence: 99%

Octa-arginine modified poly(amidoamine) dendrimers for improved delivery and cytotoxic effect of paclitaxel in cancer

Rompicharla

Kumari

Ghosh

et al. 2018

Artificial Cells, Nanomedicine, and Biotechnology

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Cell penetrating peptides (CPP) have the ability to penetrate the cell membrane and have been associated with various cargos for their facile intracellular translocation. The current study involves the synthesis of a CPP, octa-arginine (R8)-modified poly(amidoamine) dendrimer of generation 4 (G4), which has additionally been PEGylated and conjugated to the poorly soluble anticancer drug, paclitaxel (PTX). The synthesized dendrimer conjugates were characterized by proton nuclear magnetic resonance (1H-NMR) Spectroscopy and zeta potential measurements and evaluated in vitro in cell monolayers and 3D spheroids. Cellular uptake study in human cervical cancer cell line (HeLa) revealed that R8 modification significantly improved the cell association of conjugates. G4-PTX- polyethylene glycol (PEG)-R8 conjugate demonstrated enhanced cytotoxic potential and higher induction of apoptosis compared to free PTX and G4-PTX-PEG. Further, the penetrability of fluorescently labeled F-G4-PTX-PEG-R8 was evaluated in 3D spheroids of HeLa at various depths by using confocal microscopy. G4-PTX-PEG-R8 induced cell death and inhibited the growth in 3D spheroids as competently as in monolayers. The enhanced intracellular translocation of R8-modified dendrimers resulted in improved anticancer efficacy of PTX. Therefore, the newly developed dendrimer system is efficient for the intracellular delivery of PTX in cancer cells and has a strong potential to be utilized as an effective chemotherapeutic agent for cancer.

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“…Meanwhile, the stretched brush like PEG 2000 could guarantee the prior combination between the attached AEYLR and the EGFR on the cell membrane and exert the effect of AEYLR. Figure 2 also revealed the superior cellular uptake of PAR-NLC over the other ones, presented as more Cou6 signals in the cells in 1 and 4 h, the nucleic delivery of PAR-NLC was also significant which correlated closely with the outstanding membrane penetrating capacity of R8 [24]; meanwhile, the more cell internalization of PAR-NLC than R-NLC also indicated the unnegligible effect of AEYLR which targeted to the EGFR on the cell membrane.…”

Section: In Vitro Cellular Uptake Studymentioning

confidence: 86%

Polyarginine and PEG-AEYLR comodified nanostructured lipid carrier: 10mol% uncleavable PEG-AEYLR showed no shielding effect to polyarginine in vitro while maintaining good tumor targeting in vivo

Sun

Zhu

Wang

et al. 2017

Artificial Cells, Nanomedicine, and Biotechnology

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We constructed a dual ligands-modified nanostructured lipid carrier (NLC) called PAR-NLC, in which the epidermal growth factor receptor (EGFR)-targeted small peptide AEYLR was attached to the distal end of PEG anchored on the NLC surface naming PEG-AEYLR, and poly-arginine (R8) as a classic cell-penetrating peptide was attached directly to the NLC surface. PAR-NLC was near-spherical particle with average size ∼50 nm and zeta potential at +14.09 mV; the cellular uptake of PAR-NLC showed synergistic effect of the two peptides, presented as significant superior cellular uptake in EGFR-positive cells NCI-H1299 and S180 over EGFR-negative cell K562. In the animal optical imaging study, 2 h after the administration of the Dir-loaded PAR-NLC, maximum Dir signal appeared in tumor tissue, indicating prompt tumor targeting effect, as time prolonged to 48 h, the Dir signal attenuated in the organs except tumor, suggesting constant clearance from the body. In the in vivo antitumor study, in premise of the same dose, paclitaxel-loaded PAR-NLC exhibited better antitumor and safety effect than Taxol, the body weight of the mice was more stable and tumor size was smaller. In summary, PAR-NLC was a potential drug carrier to deliver anticancer drugs safely and effectively.

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RIPL peptide (IPLVVPLRRRRRRRRC)-conjugated liposomes for enhanced intracellular drug delivery to hepsin-expressing cancer cells

Cited by 35 publications

References 50 publications

Extracellular Vesicles in Cancer: Exosomes, Microvesicles and the Emerging Role of Large Oncosomes

Extracellular Vesicles in Cancer: Exosomes, Microvesicles and the Emerging Role of Large Oncosomes

Octa-arginine modified poly(amidoamine) dendrimers for improved delivery and cytotoxic effect of paclitaxel in cancer

Polyarginine and PEG-AEYLR comodified nanostructured lipid carrier: 10mol% uncleavable PEG-AEYLR showed no shielding effect to polyarginine in vitro while maintaining good tumor targeting in vivo

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