Peptide-Grafted Polymers as Artificial Converter of Cellular Signals

Intracellular 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.

[1]  G. Goss,et al.  Drug Resistance to Molecular Targeted Therapy and Its Consequences for Treatment Decisions in Non-Small-Cell Lung Cancer , 2014, Front. Oncol..

[2]  T. Niidome,et al.  Transgene regulation system responding to Rho associated coiled-coil kinase (ROCK) activation. , 2011, Journal of controlled release : official journal of the Controlled Release Society.

[3]  Makoto Hashizume,et al.  Gold nanoparticle-based colorimetric assay for cancer diagnosis. , 2010, Biosensors & bioelectronics.

[4]  T. Niidome,et al.  An intracellular kinase signal-responsive gene carrier for disordered cell-specific gene therapy. , 2006, Journal of controlled release : official journal of the Controlled Release Society.

[5]  T. Niidome,et al.  Regulation of Transgene Expression in Tumor Cells by Exploiting Endogenous Intracellular Signals , 2008, Nanoscale research letters.

[6]  A. Kishimura,et al.  Tumor accumulation of protein kinase-responsive gene carrier/DNA polyplex stabilized by alkanethiol for intravenous injection , 2015, Journal of biomaterials science. Polymer edition.

[7]  T. Niidome,et al.  Cancer-specific gene carriers responding to cancer microenvironment: Acidosis and hyper-activated protein kinases , 2013 .

[8]  T. Niidome,et al.  Peptide Substrates for Rho-Associated Kinase 2 (Rho-Kinase 2/ROCK2) , 2011, PloS one.

[9]  T. Niidome,et al.  Inflammatory cell‐specific transgene expression system responding to Iκ‐B kinase beta activation , 2009, The journal of gene medicine.

[10]  T. Niidome,et al.  Cellular signal-specific peptide substrate is essential for the gene delivery system responding to cellular signals. , 2009, Bioorganic & medicinal chemistry letters.

[11]  U. Ribel,et al.  The Mechanism of Protraction of Insulin Detemir, a Long-Acting, Acylated Analog of Human Insulin , 2004, Pharmaceutical Research.

[12]  T. Niidome,et al.  A short peptide is a protein kinase C (PKC) α‐specific substrate , 2008, Proteomics.

[13]  Mizuo Maeda,et al.  Intracellular signal-responsive artificial gene regulation for novel gene delivery. , 2002, Biomacromolecules.

[14]  T. Niidome,et al.  Protein kinase C alpha-specific peptide substrate graft-type copolymer for cancer cell-specific gene regulation systems. , 2009, Journal of controlled release : official journal of the Controlled Release Society.

[15]  T. Niidome,et al.  Effect of peptide content on the regulation of transgene expression by protein kinase Cα-responsive linear polyethylenimine-peptide conjugates. , 2014, Colloids and surfaces. B, Biointerfaces.

[16]  T. Niidome,et al.  Intracellular signal-responsive gene carrier for cell-specific gene expression. , 2005, Biomacromolecules.

[17]  T. Niidome,et al.  Design of polymeric carriers for cancer-specific gene targeting: utilization of abnormal protein kinase Calpha activation in cancer cells. , 2008, Journal of the American Chemical Society.

[18]  T. Yamaoka,et al.  Intracellular Enzyme-responsive Fragmentation of Nonviral Gene Carriers Leads to Polyplex Destabilization and Enhanced Transgene Expression , 2009 .

[19]  M. Hashizume,et al.  Improvement in the colloidal stability of protein kinase-responsive polyplexes by PEG modification. , 2012, Journal of biomedical materials research. Part A.

[20]  Felix Kratz,et al.  Impact of albumin on drug delivery--new applications on the horizon. , 2012, Journal of controlled release : official journal of the Controlled Release Society.

[21]  S. D. De Smedt,et al.  Cell division responsive peptides for optimized plasmid DNA delivery: the mitotic window of opportunity? , 2014, Journal of controlled release : official journal of the Controlled Release Society.

[22]  T. Niidome,et al.  Intracellular signal-responsive artificial gene regulation , 2006, Journal of drug targeting.

[23]  A. Kishimura,et al.  Histidinylated poly-L-lysine-based vectors for cancer-specific gene expression via enhancing the endosomal escape , 2014, Journal of biomaterials science. Polymer edition.

[24]  T. Niidome,et al.  Characterization of gene expression regulation using D-RECS polymer by enzymatic reaction for an effective design of enzyme-responsive gene regulator. , 2010, Journal of controlled release : official journal of the Controlled Release Society.

[25]  T. Niidome,et al.  Stabilization of cancer-specific gene carrier via hydrophobic interaction for a clear-cut response to cancer signaling. , 2013, Journal of controlled release : official journal of the Controlled Release Society.

[26]  A. Kishimura,et al.  A Liposome Reversibly Coated with Serum Albumin , 2014 .

[27]  T. Niidome,et al.  Molecular Mechanism of Caspase-3-Induced Gene Expression of Polyplexes Formed from Polycations Grafted with Cationic Substrate Peptides , 2009, Journal of biomaterials science. Polymer edition.

[28]  M. Maeda,et al.  A polymer micelle responding to the protein kinase a signal , 2001 .

[29]  Lin Zhu,et al.  Matrix metalloprotease 2-responsive multifunctional liposomal nanocarrier for enhanced tumor targeting. , 2012, ACS nano.

[30]  A. Kishimura,et al.  Reversal of efflux of an anticancer drug in human drug-resistant breast cancer cells by inhibition of protein kinase Cα (PKCα) activity , 2016, Tumor Biology.

[31]  T. Niidome,et al.  A hydrophilic polymer grafted with a histone tail peptide as an artificial gene regulator. , 2011, Bioorganic & medicinal chemistry.

[32]  T. Niidome,et al.  Drug delivery system based on responses to an HIV infectious signal. , 2008, Medicinal chemistry (Shariqah (United Arab Emirates)).

[33]  L. Verdone,et al.  Role of histone acetylation in the control of gene expression. , 2005, Biochemistry and cell biology = Biochimie et biologie cellulaire.

[34]  T. Niidome,et al.  Protein kinase Cα‐responsive polymeric carrier: its application for gene delivery into human cancers , 2009, Cancer science.

[35]  T. Niidome,et al.  Gene carrier showing all-or-none response to cancer cell signaling. , 2012, Journal of the American Chemical Society.

[36]  Y. Nakanishi,et al.  Serum protein kinase Cα as a diagnostic biomarker of cancers. , 2013, Cancer biomarkers : section A of Disease markers.

[37]  H Akita,et al.  Development of a novel systemic gene delivery system for cancer therapy with a tumor-specific cleavable PEG-lipid , 2007, Gene Therapy.

[38]  T. Niidome,et al.  Specific transgene expression in HIV-infected cells using protease-cleavable transcription regulator. , 2010, Journal of controlled release : official journal of the Controlled Release Society.