Effects of cell‐penetrating peptides and pegylation on transfection efficiency of polyethylenimine in mouse lungs

Nguyen, Juliane; Xie, Xiulan; Neu, Michael; Dumitrascu, Rio; Reul, Regina; Sitterberg, Johannes; Bakowsky, Udo; Schermuly, Ralph Theo; Fink, Ludger; Schmehl, Thomas; Gessler, Tobias; Seeger, Werner; Kissel, Thomas

doi:10.1002/jgm.1255

Cited by 78 publications

(45 citation statements)

References 42 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The chemical structures of polymers for polymeric nanoparticles used in pulmonary delivery systems are shown Figure 2. 26,29,38,39,[54][55][56][57]59,61,69,70,74,75,[79][80][81][82][83][84][85][86][87][88][89][90][91][92][93] Due to their biocompatibility, surface modification capability, and sustained-release properties, polymeric nanoparticles are intensively studied using various important pulmonary drugs. These pulmonary drug include antiasthmatic drugs, 22,26 antituberculosis drugs, 38,39 pulmonary hypertension drugs, 29 and anticancer drugs.…”

Section: Drugs For Inhalationmentioning

confidence: 99%

Nanomedicine in pulmonary delivery

Mansour¹,

Rhee²,

Wu³

2009

IJN

401

269

View full text Add to dashboard Cite

Section: Drugs For Inhalationmentioning

confidence: 99%

Nanomedicine in pulmonary delivery

Mansour¹,

Rhee²,

Wu³

2009

IJN

401

269

View full text Add to dashboard Cite

“…The trans-activator of transcription (TAT) peptide of human immunodeficiency virus-1 has cell-penetrating properties and the ability to deliver cargo to multiple organs (Schwarze et al, 1999). The protein transduction properties of this peptide have been exploited to facilitate intracellular delivery of a myriad of agents (Torchilin et al, 2001;Vives et al, 2003;Begley et al, 2004;Kleemann et al, 2005;Cai et al, 2006;Moschos et al, 2007;Nguyen et al, 2008;Qin et al, 2012;Bai et al, 2015).…”

Section: Introductionmentioning

confidence: 99%

Biodistribution and Efficacy of Targeted Pulmonary Delivery of a Protein Kinase C-δ Inhibitory Peptide: Impact on Indirect Lung Injury

Mondrinos

Knight

Kennedy

et al. 2015

J Pharmacol Exp Ther

View full text Add to dashboard Cite

Sepsis and sepsis-induced lung injury remain a leading cause of death in intensive care units. We identified protein kinase C-d (PKCd) as a critical regulator of the acute inflammatory response and demonstrated that PKCd inhibition was lung-protective in a rodent sepsis model, suggesting that targeting PKCd is a potential strategy for preserving pulmonary function in the setting of indirect lung injury. In this study, whole-body organ biodistribution and pulmonary cellular distribution of a transactivator of transcription (TAT)-conjugated PKCd inhibitory peptide (PKCd-TAT) was determined following intratracheal (IT) delivery in control and septic [cecal ligation and puncture (CLP)] rats to ascertain the impact of disease pathology on biodistribution and efficacy. There was negligible lung uptake of radiolabeled peptide upon intravenous delivery [,1% initial dose (ID)], whereas IT administration resulted in lung retention of .65% ID with minimal uptake in liver or kidney (,2% ID). IT delivery of a fluorescent-tagged (tetramethylrhodamine-PKCd-TAT) peptide demonstrated uniform spatial distribution and cellular uptake throughout the peripheral lung. IT delivery of PKCd-TAT at the time of CLP surgery significantly reduced PKCd activation (tyrosine phosphorylation, nuclear translocation and cleavage) and acute lung inflammation, resulting in improved lung function and gas exchange. Importantly, peptide efficacy was similar when delivered at 4 hours post-CLP, demonstrating therapeutic relevance. Conversely, spatial lung distribution and efficacy were significantly impaired at 8 hours post-CLP, which corresponded to marked histopathological progression of lung injury. These studies establish a functional connection between peptide spatial distribution, inflammatory histopathology in the lung, and efficacy of this anti-inflammatory peptide.

show abstract

“…2). The results indicated that PEGylation of the PEI complexes led to a reduction in their cytotoxicities, thereby increasing cell viability via the shielding effect of PEG [15,16]. The results also revealed that GE11-PEG-PEI had a weaker effect on the cell survival rate in vitro.…”

Section: Discussionmentioning

confidence: 77%

Peptide GE11–Polyethylene Glycol–Polyethylenimine for targeted gene delivery in laryngeal cancer

et al. 2015

View full text Add to dashboard Cite

The objective of this study was to evaluate the possibility of using GE11-polyethylene glycol-polyethylenimine (GE11-PEG-PEI) for targeted gene delivery to treat epidermal growth factor receptor (EGFR)-overexpressing laryngeal cancer. This study described the design, characterization, and in vitro and in vivo study of the nanocarrier GE11-PEG-PEI for gene delivery to treat laryngeal cancer. Analysis of the sizes and zeta potentials indicated that the formation of PEGylated complexes was dependent on the N/P ratio, and these complexes were capable of binding plasmid DNA and condensing DNA into small positively charged nanoparticles. The results also revealed that GE11-PEG-PEI had a weaker effect on cell survival in vitro. Gene transfection was performed on human laryngeal cancer Hep-2 cells in vitro and in vivo. Both the in vitro and in vivo results demonstrated that GE11-PEG-PEI had greater transfection efficiency than mPEG-PEI. Compared with mPEG-PEI/pORF-hTRAIL and saline, GE11-PEG-PEI/pORFh-TRAIL significantly (p < 0.05) reduced tumor growth in nude mice with laryngeal cancer. Moreover, the GE11-PEG-PEI/pORF-hTRAIL-treated groups showed more apoptosis than the mPEG-PEI/pORF-hTRAIL-treated groups. Therefore, our results showed that the peptide GE11 conjugated to PEG-PEI delivered significantly more genes to EGFR-overexpressing laryngeal cancer cells in vivo, indicating that GE11-PEG-PEI may be a suitable gene vector for treating EGFR-overexpressing laryngeal cancer.

show abstract

Effects of cell‐penetrating peptides and pegylation on transfection efficiency of polyethylenimine in mouse lungs

Abstract: We show that small and stable polyplex size achieved by pegylation is favourable for successful pulmonary gene delivery. Compared to PEI 25 kDa, pegylated PEI and CPP-PEG-PEI displayed enhanced transfection efficiency both in vitro and in vivo.

Cited by 78 publications

References 42 publications

Nanomedicine in pulmonary delivery

Nanomedicine in pulmonary delivery

Biodistribution and Efficacy of Targeted Pulmonary Delivery of a Protein Kinase C-δ Inhibitory Peptide: Impact on Indirect Lung Injury

Peptide GE11–Polyethylene Glycol–Polyethylenimine for targeted gene delivery in laryngeal cancer

Contact Info

Product

Resources

About