The effect of PEG-5K grafting level and particle size on tumor accumulation and cellular uptake

Lo, Chun Liang; Chou, Meng-Han; Lu, Peilin; Lo, I‐Wen; Chiang, Yi-Ting; Hung, Shang-Yu; Yang, Chieh-Yu; Lin, Shih‐Yin; Wey, Shiaw-Pyng; Lo, Jason; Hsiue, Ging‐Ho

doi:10.1016/j.ijpharm.2013.08.045

Cited by 23 publications

(11 citation statements)

References 30 publications

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“…The efficiency of the method was shown in vitro and even in animal models. Studies showed that gold nanoparticles applied intravenously to animals, harboring a human tumor xenograft composed of SK-BR-3 cells, allowed a complete elimination of the tumor by an optical activation of the gold nanoparticles 10 – 12 . The challenge of this approach is to achieve a specific targeting of gold nanoparticles onto the cancer cells.…”

Section: Introductionmentioning

confidence: 99%

Functionalization of gold-nanoparticles by the Clostridium perfringens enterotoxin C-terminus for tumor cell ablation using the gold nanoparticle-mediated laser perforation technique

Becker

Leskau

Schlingmann-Molina

et al. 2018

Sci Rep

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A recombinant produced C-terminus of the C. perfringens enterotoxin (C-CPE) was conjugated to gold nanoparticles (AuNPs) to produce a C-CPE-AuNP complex (C-CPE-AuNP). By binding to claudins, the C- CPE should allow to target the AuNPs onto the claudin expressing tumor cells for a subsequent cell killing by application of the gold nanoparticle-mediated laser perforation (GNOME-LP) technique. Using qPCR and immunocytochemistry, we identified the human Caco-2, MCF-7 and OE-33 as well as the canine TiHoDMglCarc1305 as tumor cells expressing claudin-3, -4 and -7. Transepithelial electrical resistance (TEER) measurements of Caco-2 cell monolayer showed that the recombinant C-CPE bound to the claudins. GNOME-LP at a laser fluence of 60 mJ/cm2 and a scanning speed of 0.5 cm/s specifically eliminated more than 75% of claudin expressing human and canine cells treated with C-CPE-AuNP. The same laser fluence did not affect the cells when non-functionalized AuNPs were used. Furthermore, most of the claudin non-expressing cells treated with C-CPE-AuNP were not killed by GNOME-LP. Additionally, application of C-CPE-AuNP to spheroids formed by MCF-7 and OE-33 cells grown in Matrigel reduced spheroid area. The results demonstrate that specific ablation of claudin expressing tumor cells is efficiently increased by activated C-CPE functionalized AuNPs using optical methods.

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Section: Introductionmentioning

confidence: 99%

Functionalization of gold-nanoparticles by the Clostridium perfringens enterotoxin C-terminus for tumor cell ablation using the gold nanoparticle-mediated laser perforation technique

Becker

Leskau

Schlingmann-Molina

et al. 2018

Sci Rep

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“…As a result, tumor accumulation (24 h AUC) for 20 nm and 60-100 nm PEG-modified AuNPs were 0.3% and 17.0-26.5% ID, respectively. 84 Similarly, Lo et al 85 observed that the amount of 40 nm PEG-modified AuNPs in tumor tissue declined with time, indicating that these particles are small enough to be washed out from the extracellular matrix of the tumor. These studies suggest that tumor-enhanced penetration and retention effect is applicable only for large particles.…”

Section: Distribution To the Tumor Tissuementioning

confidence: 96%

Pharmacokinetics of metallic nanoparticles

Lin

Monteiro‐Riviere

Riviere

2014

WIREs Nanomed Nanobiotechnol

186

138

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Metallic nanoparticles (NPs) have been widely applied in the field of nanomedicine. A comprehensive understanding of their pharmacokinetics is crucial for proper risk assessment and safe biomedical applications. This review focuses on gold and silver (Ag) NPs, and briefly discusses iron oxide, titanium dioxide (TiO2 ), and zinc oxide NPs. Pharmacokinetics of metallic NPs depends on the particle type, size, surface charge, surface coating, protein binding, exposure route, dose, and species. Generally, blood half-life is shorter in rodents than in larger laboratory animals (e.g., rabbits or monkeys) and differs between intravenous and oral exposures. Oral, dermal, or inhalational absorption is low (≤5%), but may increase with smaller sizes, negative charge, and appropriate coatings. Metallic NPs can be distributed throughout the body, primarily accumulating in the liver, spleen, and lymph node due to nonspecific uptake by reticuloendothelial cells, and could remain in the body for ≥6 months. Metallic NPs (≤100 nm) can cross the blood-brain barrier (BBB), favored by coating with BBB-permeable neuropeptides. Placental transfer depends on the stage of embryonic/placental maturation and surface composition, and may be enhanced by coating with biocompatible molecules (e.g., ferritin or polyethylene glycol). Renal and biliary excretion is generally low due to persistent accumulation in tissues, but renal elimination could be substantially increased with smaller sizes and specific coatings (e.g., glutathione). Physiologically based pharmacokinetic models for gold/dendrimer composite nanodevices, AgNPs, and TiO2 NPs have been developed in rats and the AgNP and TiO2 NP models have been extrapolated to humans to support risk assessment and nanomedicine applications.

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“…Although equipped with angiogenesis, tumor tissue still experiences far less blood than the reticuloendothelial system (RES) [1], in this case to prepare nanoparticles (NPs) that are less captured by the RES could prolong their systemic circulation time and improve the chances to enter the tumor tissue [2]. Since PEG could form a layer of neutral generic hydrophilic polymer outside of the NPs, PEGylated NPs could exhibit stealth effect towards RES thus extending the circulation time and adding the chances to enter the tumor tissue [3][4][5].…”

Section: Introductionmentioning

confidence: 99%

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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The effect of PEG-5K grafting level and particle size on tumor accumulation and cellular uptake

Cited by 23 publications

References 30 publications

Functionalization of gold-nanoparticles by the Clostridium perfringens enterotoxin C-terminus for tumor cell ablation using the gold nanoparticle-mediated laser perforation technique

Functionalization of gold-nanoparticles by the Clostridium perfringens enterotoxin C-terminus for tumor cell ablation using the gold nanoparticle-mediated laser perforation technique

Pharmacokinetics of metallic nanoparticles

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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