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

Ren, Henglei; Zhou, Liang; Liu, Min; Lu, Weiyue; Gao, Chunli

doi:10.1007/s12032-015-0624-9

Cited by 14 publications

(13 citation statements)

References 21 publications

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“…98 PEI and GE11 were bound using a heterobifunctional PEG (maleimide–PEG–NHS), where the amino group of GE11 was coupled to the NHS group to obtain GE11–PEG–maleimide, which was then coupled with PEI using the maleimide amino reaction to obtain GE11–PEG–PEI. 98 To formulate NPs, GE11–PEG–PEI was further complexed with a TRAIL-encoding plasmid via electrostatic interactions. 98 Both in vitro and in vivo , the modified NPs significantly increased gene transfection efficiency and inhibited Hep-2 cell tumor growth in mice compared to unmodified NPs.…”

Section: Polymeric Nanoparticlesmentioning

confidence: 99%

Nanoparticles for Immune Cytokine TRAIL-Based Cancer Therapy

et al. 2018

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The immune cytokine tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) has received significant attention as a cancer therapeutic due to its ability to selectively trigger cancer cell apoptosis without causing toxicity in vivo. While TRAIL has demonstrated significant promise in preclinical studies in mice as a cancer therapeutic, challenges including poor circulation half-life, inefficient delivery to target sites, and TRAIL resistance have hindered clinical translation. Recent advances in drug delivery, materials science, and nanotechnology are now being exploited to develop next-generation nanoparticle platforms to overcome barriers to TRAIL therapeutic delivery. Here, we review the design and implementation of nanoparticles to enhance TRAIL-based cancer therapy. The platforms we discuss are diverse in their approaches to the delivery problem and provide valuable insight into guiding the design of future nanoparticle-based TRAIL cancer therapeutics to potentially enable future translation into the clinic.

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Section: Polymeric Nanoparticlesmentioning

confidence: 99%

Nanoparticles for Immune Cytokine TRAIL-Based Cancer Therapy

et al. 2018

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“…Interfering with this pathway using monoclonal antibodies or tyrosine kinase inhibitors have been extensively examined, but clinical trials with these drugs have been less than promising. However, the overexpression of EGFR in various cancers is also being exploited as a method to deliver therapeutics via NP-based platforms [40–43]. Multiple non-targeted nanotherapeutics have been clinically examined for the treatment of TNBC, including paclitaxel-embedded liposomes and IT-101 (a camptothecin-conjugated cyclodextrin polymeric NP) [44].…”

Section: Discussionmentioning

confidence: 99%

Aminoflavone-loaded EGFR-targeted unimolecular micelle nanoparticles exhibit anti-cancer effects in triple negative breast cancer

et al. 2016

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Triple negative breast cancer (TNBC) is an aggressive subtype of breast cancer for which there is no available targeted therapy. TNBC cases contribute disproportionately to breast cancer-related mortality, thus the need for novel and effective therapeutic methods is urgent. We have previously shown that a National Cancer Institute (NCI) investigational drug aminoflavone (AF) exhibits strong growth inhibitory effects in TNBC cells. However, in vivo pulmonary toxicity resulted in withdrawal or termination of several human clinical trials for AF. Herein we report the in vivo efficacy of a nanoformulation of AF that enhances the therapeutic index of AF in TNBC. We engineered a unique unimolecular micelle nanoparticle (NP) loaded with AF and conjugated with GE11, a 12 amino acid peptide targeting epidermal growth factor receptor (EGFR), since EGFR amplification is frequently observed in TNBC tumors. These unimolecular micelles possessed excellent stability and preferentially released drug payload at endosomal pH levels rather than blood pH levels. Use of the GE11 targeting peptide resulted in enhanced cellular uptake and strong growth inhibitory effects in TNBC cells. Further, AF-loadedloaded, GE11-lacking, GE11-conjugated (targeted) unimolecular micelle NPs significantly inhibit orthotopic TNBC tumor growth in a xenograft model, compared to treatment with AF-loaded, GE11-lacking (non-targeted) unimolecular micelle NPs or free AF. Interestingly, the animals treated with AF-loaded, targeted NPs had the highest plasma and tumor level of AF among different treatment groups yet exhibited no increase in plasma aspartate aminotransferase (AST) activity level or observable tissue damage at the time of sacrifice. Together, these results highlight AF-loaded, EGFR-targeted unimolecular micelle NPs as an effective therapeutic option for EGFR-overexpressing TNBC.

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“…In vitro gene transfection efficiency can reach up to 47% while retaining in vivo antitumor efficacy. 26 Another novel mechanism for delivery involves systemically administered, ultrasound-guided microbubbles targeting HNSCC tumors. Vigorous mixing of aqueous solutions of lipid and nucleic acid generates microbubbles with a lipid shell and perfluorobutane gas interior.…”

Section: Gene Delivery Systemsmentioning

confidence: 99%

Nucleic acid targeting: towards personalized therapy for head and neck cancer

2015

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In light of a detailed characterization of genetic aberrations in cancer, nucleic acid targeting represents an attractive therapeutic approach with significant translational potential. Head and neck squamous cell carcinoma (HNSCC) is a leading cause of cancer deaths worldwide with stagnant 5-year survival rates. Advances in conventional treatment have done little to improve survival and combined chemoradiation is associated with significant adverse effects. Recent reports have characterized the genetic alterations in HNSCC and demonstrated that mutations confer resistance to conventional and molecular targeted therapies. The ability to use specific nucleic acid sequences to inhibit cancer-associated genes including non-druggable targets facilitates personalized medicine approaches with less adverse effects. Additionally, advances in drug delivery mechanisms have increased the transfection efficiency aiding in greater therapeutic responses. Given these advances, the stage has been set to translate the information garnered from genomic studies into personalized treatment strategies. Genes involved in the tumor protein 53 (TP53) and epidermal growth factor receptor (EGFR) pathways have been extensively investigated and many promising preclinical studies have shown tumor inhibition through genetic modulation. We, and others, have demonstrated that targeting oncogene expression with gene therapy approaches is feasible in patients. Other methods such as RNA interference have proven to be effective and are potential candidates for clinical studies. This review summarizes the major advances in sequence-specific gene modulation in the preclinical setting and in clinical trials in head and neck cancer patients.

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

Cited by 14 publications

References 21 publications

Nanoparticles for Immune Cytokine TRAIL-Based Cancer Therapy

Nanoparticles for Immune Cytokine TRAIL-Based Cancer Therapy

Aminoflavone-loaded EGFR-targeted unimolecular micelle nanoparticles exhibit anti-cancer effects in triple negative breast cancer

Nucleic acid targeting: towards personalized therapy for head and neck cancer

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