Effect of peptide content on the regulation of transgene expression by protein kinase Cα-responsive linear polyethylenimine-peptide conjugates

Toita, Riki; Kang, Jeong Hun; Kim, Chan Woo; Shiosaki, Shujiro; Mori, Takeshi; Niidome, Takuro; Katayama, Yoshiki

doi:10.1016/j.colsurfb.2014.09.004

Cited by 5 publications

(8 citation statements)

References 45 publications

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“…The answer to explain this results may be that the factor to suppress gene transcription is not the peptide, but is the fraction of polymer backbone which does not bind directly to DNA strand. 29,31 Actually, a similar tendency was also observed in Caspase-3 responsive polymers. 30 Lower content of the peptide side chains gave stronger suppression of gene expression in the polypex.…”

Section: Mechanism Of Gene Regulation In D-recs Systemssupporting

confidence: 69%

“…If suppression of transcription and its recovery in response to target PKCα are investigated by using LPEI-type PKCα-responsive polymers with various peptide contents, interesting results are obtained (Table 1). 31 When the peptide content was relatively low (ca. 4 mol %), PKCα response, which is the expression ratio between LPEI(S) and LPEI(A), was only 2.6 fold.…”

Section: Mechanism Of Gene Regulation In D-recs Systemsmentioning

confidence: 99%

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Peptide-Grafted Polymers as Artificial Converter of Cellular Signals

Katayama¹

2016

Bulletin of the Chemical Society of Japan

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and also a member of three research centers in Kyushu University. He also is an adjunct professor of Chung Yuan Christian University, Taiwan. His current scientific interests are development of molecular systems for medical use including bioimaging, diagnostic, DDS, immune-modulating systems. He is now eager to create new research field tying basic life science and clinical medicine. AbstractIntracellular signal transduction systems consisting of sophisticated molecular networks are essential to provide almost all cellular functions. Any abnormal activation of enzymes included in this network can be directly linked to various disease states. Therefore, cellular function can be altered if we can modulate this signal transduction process. In this context, artificial signal converters, which respond to particular abnormal signaling to activate transgene transcription, are introduced. Such molecular systems use polymer materials grafted with cationic peptides, which are a specific substrate of target protein kinase or protease. This concept which is called D-RECS, DDS in response to cellular signals, could have potential for design of disease cell specific therapeutic or diagnostic (imaging) systems using pathological signaling as a target. Molecular design and structural factors affecting signal response in such systems are discussed.

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Section: Mechanism Of Gene Regulation In D-recs Systemssupporting

confidence: 69%

Section: Mechanism Of Gene Regulation In D-recs Systemsmentioning

confidence: 99%

Peptide-Grafted Polymers as Artificial Converter of Cellular Signals

Katayama¹

2016

Bulletin of the Chemical Society of Japan

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“…Histone-modified PEI as a carrier showed low cytotoxicity and could effectively bind and condense pDNA. Katayama et al found that PEI could be modified with different types of peptides through click chemistry in response to PKCα ( Figure 6 ) [ 77 ]. The content and quantity of peptide in PEI/peptide conjugates had significant effects on gene transfection.…”

Section: Pei Modificationsmentioning

confidence: 99%

Section: Figurementioning

confidence: 99%

Polyethyleneimine-Based Drug Delivery Systems for Cancer Theranostics

Zhao

Zhou

2022

JFB

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With the development of nanotechnology, various types of polymer-based drug delivery systems have been designed for biomedical applications. Polymer-based drug delivery systems with desirable biocompatibility can be efficiently delivered to tumor sites with passive or targeted effects and combined with other therapeutic and imaging agents for cancer theranostics. As an effective vehicle for drug and gene delivery, polyethyleneimine (PEI) has been extensively studied due to its rich surface amines and excellent water solubility. In this work, we summarize the surface modifications of PEI to enhance biocompatibility and functionalization. Additionally, the synthesis of PEI-based nanoparticles is discussed. We further review the applications of PEI-based drug delivery systems in cancer treatment, cancer imaging, and cancer theranostics. Finally, we thoroughly consider the outlook and challenges relating to PEI-based drug delivery systems.

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“…To achieve the cancer specific gene expression, intelligent polymeric carriers have been reported to deliver and release therapeutic genes in response to cancer-specific environmental stimuli, such as acidic pH, [3] redox environment, [4][5][6][7][8] and enzymes. [9][10][11][12][13] As cancer-specific environments, we have focused on protein kinases (PKs), which are abnormally activated in cancer cells to induce cancer-specific signal transduction. [14,15] We have developed polymeric carriers grafted with substrate peptides for PKs.…”

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confidence: 99%

Tumor accumulation of protein kinase-responsive gene carrier/DNA polyplex stabilized by alkanethiol for intravenous injection

Sato

Kim

et al. 2015

Journal of Biomaterials Science, Polymer Edition

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We synthesized polymeric gene carriers consisting of poly-L-lysine (PLL) main chain modified both with substrate peptide for protein kinase Cα (PKCα) and alkanethiol (pentadecanethiol). Due to the grafted substrate peptide, the polyplex prepared from these carriers is expected to show gene expression triggered by the phosphorylation of the peptide by intracellular PKCα. The modified alkanethiol on the main chain stabilized the polyplex both via disulfide crosslinking and hydrophobic interaction. The polyplex found to show gene expression in vitro when the alkanethiol content in the main chain was enough low (4-mol%-modification of PLL's ε-amine group) to minimize cytotoxic effect. Even though the content of alkanethiol is low, the polyplex had significant stability in a model serum solution and showed longer blood circulation in vivo. The polyplex clearly accumulated in tumor after intravenous injection.

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Effect of peptide content on the regulation of transgene expression by protein kinase Cα-responsive linear polyethylenimine-peptide conjugates

Cited by 5 publications

References 45 publications

Peptide-Grafted Polymers as Artificial Converter of Cellular Signals

Peptide-Grafted Polymers as Artificial Converter of Cellular Signals

Polyethyleneimine-Based Drug Delivery Systems for Cancer Theranostics

Tumor accumulation of protein kinase-responsive gene carrier/DNA polyplex stabilized by alkanethiol for intravenous injection

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