Poly(ε-caprolactone)-containing graft copolymers for ratiometric extracellular oxygen sensing

Abstract A graft copolymer composed of poly(e-caprolactone) as a hydrophobic chain and poly(N-(2-hydroxypropyl)methacrylamide) as a hydrophilic segment with an internal reference probe for oxygen sensing was prepared. Highly efficient platinum(II)meso-tetra(pentafluorophenyl)porphine (PtTFPP) was used as a typical oxygen probe. Although PtTFPP was highly efficient, it is hydrophobic, limiting its direct application for oxygen sensing in biological conditions. By using the amphiphilic graft copolymer, PTTFPP was successfully incorporated into the micelles formed by this polymer to not only enable the application of PtTFPP for biosensing in medium but also retain its high efficiency. The quantum efficiency of PtTFPP in the micelle solution under nitrogen can reach as high as 0.20. The PtTFPP-containing micelles were tested for high throughput cell respiration and bacteria detection. The influence of an antibiotic, antimycin as a representative example, on cell respiration was also studied. For achieving high accurate sensing, an internal built-in reference probe with aggregation induced emission properties were also polymerized in the graft copolymer. This study demonstrated that the graft polymer approach is a good way to enable highly efficient and hydrophobic oxygen probes for biosensing.

[1]  Xiong-Zhi Wu,et al.  Hypoxia and hepatocellular carcinoma: The therapeutic target for hepatocellular carcinoma , 2007, Journal of gastroenterology and hepatology.

[2]  Michael Kasha,et al.  Energy Transfer Mechanisms and the Molecular Exciton Model for Molecular Aggregates1, 2 , 1963 .

[3]  M. Tanihara,et al.  Synthesis and photocytotoxicity of S-glucosylated 5,10,15,20-Tetrakis(tetrafluorophenyl)porphyrin metal complexes as efficient (1)O(2)-generating glycoconjugates. , 2009, Bioconjugate chemistry.

[4]  Chi K. Chang,et al.  Electronic spectroscopy, photophysical properties, and emission quenching studies of an oxidatively robust perfluorinated platinum porphyrin. , 2004, Inorganic chemistry.

[5]  Yordan Kostov,et al.  Dual Excitation Ratiometric Fluorescent pH Sensor for Noninvasive Bioprocess Monitoring: Development and Application , 2002, Biotechnology progress.

[6]  Pierre Hainaut,et al.  Targeting the hallmarks of cancer: towards a rational approach to next-generation cancer therapy. , 2013, Current opinion in oncology.

[7]  D. Meldrum,et al.  A New Crosslinkable Oxygen Sensor Covalently Bonded into Poly(2-hydroxyethyl methacrylate)-CO-Polyacrylamide Thin Film for Dissolved Oxygen Sensing. , 2010, Chemistry of materials : a publication of the American Chemical Society.

[8]  Daniel T Chiu,et al.  Highly fluorescent semiconducting polymer dots for biology and medicine. , 2013, Angewandte Chemie.

[9]  Xianfeng Zhou,et al.  An FRET-based ratiometric chemosensor for in vitro cellular fluorescence analyses of pH. , 2012, Biomaterials.

[10]  G. Semenza.  Oxygen sensing, homeostasis, and disease. , 2011, New England Journal of Medicine.

[11]  Changfeng Wu,et al.  Ratiometric single-nanoparticle oxygen sensors for biological imaging. , 2009, Angewandte Chemie.

[12]  Xi Chen,et al.  ORMOSIL oxygen sensors on polystyrene microplate for dissolved oxygen measurement , 2007 .

[13]  D. Webster,et al.  Cell growth and oxygen uptake of Escherichia coli and Pseudomonas aeruginosa are differently effected by the genetically engineered Vitreoscilla hemoglobin gene. , 2001, Journal of biotechnology.

[14]  Peter Carmeliet,et al.  Hypoxia and inflammation. , 2011, The New England journal of medicine.

[15]  Dai Fukumura,et al.  Micelle-Encapsulated Quantum Dot-Porphyrin Assemblies as in Vivo Two-Photon Oxygen Sensors. , 2015, Journal of the American Chemical Society.

[16]  M. Holl,et al.  New ratiometric optical oxygen and pH dual sensors with three emission colors for measuring photosynthetic activity in Cyanobacteria. , 2011, Journal of materials chemistry.

[17]  Jamshidi,et al.  Conjugated 1,10-Phenanthrolines as Tunable Fluorophores. , 1999, Angewandte Chemie.

[18]  D. Meldrum,et al.  A series of poly[N-(2-hydroxypropyl)methacrylamide] copolymers with anthracene-derived fluorophores showing aggregation-induced emission properties for bioimaging. , 2012, Journal of polymer science. Part A, Polymer chemistry.

[19]  O. Wolfbeis,et al.  Optical methods for sensing and imaging oxygen: materials, spectroscopies and applications. , 2014, Chemical Society reviews.

[20]  Deqing Zhang,et al.  The convenient fluorescence turn-on detection of heparin with a silole derivative featuring an ammonium group. , 2008, Chemical communications.

[21]  D. Hanahan,et al.  Hallmarks of Cancer: The Next Generation , 2011, Cell.

[22]  S. Nie,et al.  In vivo cancer targeting and imaging with semiconductor quantum dots , 2004, Nature Biotechnology.

[23]  Ryan T. K. Kwok,et al.  Aggregation-Induced Emission: Together We Shine, United We Soar! , 2015, Chemical reviews.

[24]  Emiri T. Mandeville,et al.  Two-photon high-resolution measurement of partial pressure of oxygen in cerebral vasculature and tissue , 2010, Nature Methods.

[25]  D. Meldrum,et al.  Dually Fluorescent Core-Shell Microgels for Ratiometric Imaging in Live Antigen-Presenting Cells , 2014, PloS one.

[26]  Dmitri B Papkovsky,et al.  Sensing intracellular oxygen using near-infrared phosphorescent probes and live-cell fluorescence imaging. , 2007, American journal of physiology. Regulatory, integrative and comparative physiology.

[27]  G. Semenza.  Hypoxia-inducible factor 1: regulator of mitochondrial metabolism and mediator of ischemic preconditioning. , 2011, Biochimica et biophysica acta.

[28]  F. Marshall,et al.  In vivo molecular and cellular imaging with quantum dots. , 2005, Current opinion in biotechnology.

[29]  C. Peers,et al.  Hypoxia and Alzheimer's disease. , 2007, Essays in biochemistry.

[30]  Otto S. Wolfbeis,et al.  Materials for fluorescence-based optical chemical sensors , 2005 .

[31]  D A Hilton,et al.  Overexpression of hypoxia-inducible factor 1alpha in common human cancers and their metastases. , 1999, Cancer research.

[32]  Deirdre R. Meldrum,et al.  Nanostructured Oxygen Sensor - Using Micelles to Incorporate a Hydrophobic Platinum Porphyrin , 2012, PloS one.

[33]  D. Meldrum,et al.  Utilization of micelles formed from poly(ethylene glycol)-block-poly(epsilon-caprolactone) block copolymers as nanocarriers to enable hydrophobic red two-photon absorbing emitters for cells imaging. , 2009, Journal of biomedical materials research. Part A.

[34]  M. Ducros,et al.  Simultaneous two-photon imaging of oxygen and blood flow in deep cerebral vessels , 2011, Nature Medicine.

[35]  M. Ashcroft,et al.  Targeting the molecular basis for tumour hypoxia , 2005, Expert Reviews in Molecular Medicine.

[36]  Otto S. Wolfbeis,et al.  Self-referenced RGB colour imaging of intracellular oxygen , 2011 .

[37]  J. Hodsoll,et al.  Frequency of nocturnal hypoxia in clinically stable patients during stroke rehabilitation , 2010, Clinical rehabilitation.

[38]  M. Asaka,et al.  Constitutive expression of hypoxia-inducible factor-1alpha renders pancreatic cancer cells resistant to apoptosis induced by hypoxia and nutrient deprivation. , 2001, Cancer research.

[39]  G. Semenza.  mechanisms of disease Oxygen Sensing , Homeostasis , and Disease , 2011 .

[40]  Katrin Marcus,et al.  Regulation of mitochondrial respiration and apoptosis through cell signaling: cytochrome c oxidase and cytochrome c in ischemia/reperfusion injury and inflammation. , 2012, Biochimica et biophysica acta.

[41]  B. Tang,et al.  Fluorescent chemosensor for detection and quantitation of carbon dioxide gas. , 2010, Journal of the American Chemical Society.

[42]  Muhammad Hanafi,et al.  Synthesis and biological activity of 2-hydroxynicotinoyl-serine-butyl esters related to antibiotic UK-3A. , 2010, Bioorganic & medicinal chemistry letters.

[43]  J. Aylott,et al.  A real-time ratiometric method for the determination of molecular oxygen inside living cells using sol-gel-based spherical optical nanosensors with applications to rat C6 glioma. , 2001, Analytical chemistry.

[44]  D. Meldrum,et al.  Ratiometric fluorescent pH-sensitive polymers for high-throughput monitoring of extracellular pH. , 2016, RSC advances.

[45]  D. Meldrum,et al.  Using fluorine-containing amphiphilic random copolymers to manipulate the quantum yields of aggregation-induced emission fluorophores in aqueous solutions and the use of these polymers for fluorescent bioimaging. , 2012, Journal of materials chemistry.

[46]  Ging-Ho Hsiue,et al.  Preparation and characterization of intelligent core-shell nanoparticles based on poly(D,L-lactide)-g-poly(N-isopropyl acrylamide-co-methacrylic acid). , 2005, Journal of controlled release : official journal of the Controlled Release Society.

[47]  Dmitri B. Papkovsky,et al.  Phosphorescent oxygen-sensitive materials for biological applications , 2005 .

[48]  H. Clark,et al.  Production, characteristics and applications of fluorescent PEBBLE nanosensors : Potassium, oxygen, calcium and pH imaging inside live cells : Biomedical applications , 2002 .

[49]  S. Fulda,et al.  Role of hypoxia inducible factor-1 alpha in modulation of apoptosis resistance , 2007, Oncogene.

[50]  Frank J Giordano,et al.  Oxygen, oxidative stress, hypoxia, and heart failure. , 2005, The Journal of clinical investigation.

[51]  A. Bhunia,et al.  Hypoxia and chronic lung disease , 2007, Journal of Molecular Medicine.

[52]  Lise Arleth,et al.  In vitro characterization of PEGylated phospholipid micelles for improved drug solubilization: effects of PEG chain length and PC incorporation. , 2004, Journal of pharmaceutical sciences.

[53]  Ingo Klimant,et al.  Poly(styrene-block-vinylpyrrolidone) beads as a versatile material for simple fabrication of optical nanosensors. , 2008, Analytical chemistry.

[54]  Alexander I. Karagodov,et al.  Two new "protected" oxyphors for biological oximetry: properties and application in tumor imaging. , 2011, Analytical chemistry.

[55]  Erich Gnaiger,et al.  Biphasic Oxygen Kinetics of Cellular Respiration and Linear Oxygen Dependence of Antimycin A Inhibited Oxygen Consumption , 2004, Molecular Biology Reports.

[56]  Qiang Zhao,et al.  Fluorescent/phosphorescent dual-emissive conjugated polymer dots for hypoxia bioimaging† †Electronic supplementary information (ESI) available. See DOI: 10.1039/c4sc03062a Click here for additional data file. , 2015, Chemical science.

[57]  O. Wolfbeis,et al.  Ultra-small, highly stable, and sensitive dual nanosensors for imaging intracellular oxygen and pH in cytosol. , 2012, Journal of the American Chemical Society.

[58]  Jean M. J. Fréchet,et al.  Light-harvesting dendrimers , 2000 .

[59]  Yongqiang Dong,et al.  Label-free fluorescent probing of G-quadruplex formation and real-time monitoring of DNA folding by a quaternized tetraphenylethene salt with aggregation-induced emission characteristics. , 2008, Chemistry.