Elektroaktiv Polymer Nanopartikler udstiller fototermisk Properties
Summary
A protocol is presented for the synthesis and preparation of nanoparticles consisting of electroactive polymers.
Abstract
A method for the synthesis of electroactive polymers is demonstrated, starting with the synthesis of extended conjugation monomers using a three-step process that finishes with Negishi coupling. Negishi coupling is a cross-coupling process in which a chemical precursor is first lithiated, followed by transmetallation with ZnCl2. The resultant organozinc compound can be coupled to a dibrominated aromatic precursor to give the conjugated monomer. Polymer films can be prepared via electropolymerization of the monomer and characterized using cyclic voltammetry and ultraviolet-visible-near infrared (UV-Vis-NIR) spectroscopy. Nanoparticles (NPs) are prepared via emulsion polymerization of the monomer using a two-surfactant system to yield an aqueous dispersion of the polymer NPs. The NPs are characterized using dynamic light scattering, electron microscopy, and UV-Vis-NIR-spectroscopy. Cytocompatibility of NPs is investigated using the cell viability assay. Finally, the NP suspensions are irradiated with a NIR laser to determine their effectiveness as potential materials for photothermal therapy (PTT).
Introduction
Elektroaktive polymerer ændre deres egenskaber (farve, ledningsevne, reaktivitet, volumen, etc.) i nærvær af et elektrisk felt. De hurtige skift gange, justerbarhed, holdbarhed og letvægts karakteristika af elektroaktive polymerer har ført til mange foreslåede programmer, herunder alternativ energi, sensorer, electrochromics og biomedicinsk udstyr. Elektroaktive polymerer er potentielt anvendelige som fleksible, letvægts batteri og kondensator elektroder. 1 Anvendelser af elektroaktive polymerer i elektrochrome enheder omfatter systemer til bygninger og biler, solbriller, beskyttelsesbriller, optiske lagringsenheder og intelligente tekstiler blænding reduktion. 2-5 Smart vinduer kan reducere energibehovet ved at blokere bestemte bølgelængder af lys on-demand og beskytte interiører af boliger og biler. Intelligente tekstiler kan bruges i tøj for at hjælpe med at beskytte mod UV-stråling. 6 Elektroaktive polymerer har also begyndt at blive anvendt i medicinsk udstyr. Blandt elektroaktive polymerer, der anvendes i biomedicinske indretninger, polypyrrol (PPy), polyanilin (PANI) og poly (3,4-ethylenedioxythiophene) (PEDOT) er blandt de mest almindelige. For eksempel er disse typer af polymerer almindeligvis anvendes som transducere i biosensor enheder 7 Anvendelser i terapeutisk levering har også vist sig lovende.; undersøgelser har vist frigivelse af lægemidler og terapeutiske proteiner fra enheder fremstillet ud fra elektroaktive polymerer. 8-12 For nylig har elektroaktive polymerer blevet anvendt som terapeutiske midler i fototermisk terapi. 13-15 I fototermisk behandling, skal fototermisk midler absorberer lys i den nærmeste -Infrarød (NIR) område (~ 700-900 nm), også kendt som det terapeutiske vindue, hvor lyset har den maksimale indtrængningsdybde i væv, typisk op til 1 cm. 16,17 I dette område, biologiske kromoforer, såsom hæmoglobin , iltet hæmoglobin, lipider og vand har ringe-til-noabsorbans, som gør det muligt let at trænge let. Når fototermisk agenter absorberer lys i denne terapeutiske vindue er photoenergy konverteret til fototermisk energi.
Irvin og medarbejdere har tidligere rapporteret alkoxysubstitueret bis-EDOT benzen monomerer, blev syntetiseret under anvendelse Negishi kobling. 18 Negishi kobling er en foretrukken fremgangsmåde til carbon-carbonbinding formation. Denne fremgangsmåde har mange fordele, herunder brugen af organozinkreagenser mellemprodukter, som er mindre toksiske og har tendens til at have højere reaktivitet end andre organometalliske anvendes. 19,20 organozinkforbindelser er også kompatible med en lang række funktionelle grupper på de organohalogenider. 20 I Negishi koblingsreaktion er en organohalide og organometallisk koblet ved anvendelse af en palladium (0) katalysator. 20 I arbejdet præsenteret heri, er denne krydskobling fremgangsmåde anvendes i syntesen af 1,4-dialkoxy-2,5-bis ( 3,4-ethylenedioxythienyl) benzene (BEDOT-B (OR) 2) monomerer. Disse monomerer kan derefter let polymeriseres elektrokemisk eller kemisk til dannelse af polymerer, der er lovende kandidater til anvendelse i biomedicinske anvendelser.
Konventionelle fremgangsmåder til fremstilling af kolloide suspensioner polymere i vandige opløsninger til biomedicinske anvendelser omfatter typisk opløsning af bulk polymerer efterfulgt af nanoprecipitation eller emulsion-opløsningsmiddelafdampning teknikker. 21,22 For at fremstille NPs af poly (BEDOT-B (OR) 2) , en bottom-up-tilgang demonstreres her, hvor de nationale parlamenter syntetiseres via de situ emulsionspolymerisering. Emulsionspolymerisation er en proces, der er let skalerbar og er en relativt hurtig metode til fremstilling NP. 22 Undersøgelser med emulsionspolymerisation at producere NPs andre elektroaktive polymerer er blevet rapporteret for PPv og PEDOT. 15,23,24 PEDOT NP, f.eks er udarbejdet efter spray emulsion polymerization. 24 Denne fremgangsmåde er vanskelig at reproducere og giver typisk større, mikrometerstore partikler. Den beskrives i denne artikel protokol udforsker brugen af en drop-lydbehandling metode til reproducerbart forberede 100-nm polymer NP'er.
I denne protokol, elektroaktive polymerer skræddersyet til at absorbere lys i NIR-området svarende til tidligere rapporterede poly (BEDOT-B (OR) 2) syntetiseres og karakteriseres til at demonstrere deres potentiale i elektrokrome indretninger og som TOT agenter. For det første er protokollen for syntese af monomerer via Negishi kobling beskrevet. Monomererne karakteriseres ved NMR og UV-Vis-NIR-spektroskopi. Fremstillingen af kolloide suspensioner NP via oxidativ emulsionspolymerisation i vandige medier er også beskrevet. Proceduren er baseret på tidligere beskrevet af Han et al., Der anvendes på de forskellige monomerer en totrins emulsionspolymerisationsproces. En to-overfladeaktive system erbruges til at styre NP monodispersitet. En celleviabilitetstest anvendes til at vurdere cytocompatibility af NPS. Endelig er potentialet i disse nationale parlamenter til at fungere som TOT transducere demonstreret ved bestråling med en NIR laser.
Protocol
Representative Results
Discussion
I dette arbejde, har elektroaktive polymer NP'er blevet syntetiseret som potentielle PTT midler til cancerbehandling. Fremstillingen af NPS er beskrevet, startende med syntesen af monomererne efterfulgt af emulsionspolymerisation. Mens fremstillingen af NP'er ved hjælp elektroaktive polymerer, såsom EDOT og pyrrol er blevet beskrevet før, dette papir beskriver fremstillingen af polymere NP'er startende med unikke udvidede konjugationsfremgangsmåder monomerer, hvilket viser, at den…
Declarações
The authors have nothing to disclose.
Acknowledgements
Dette arbejde blev finansieret delvist af Texas Emerging Technology Fund (Opstart til TB), Texas State University Research Enhancement Program, Texas State University Ph.d. Research Fellowship (til TC), NSF Partnerskab for forskning og uddannelse i Materials (PREM, DMR-1205670), Welch Foundation (AI-0045) og National Institutes of Health (R01CA032132).
Materials
| 2 mm diameter platinum working electrode | CH Instruments | CH102 | Polished using very fine sandpaper |
| 3,4-ethylenedioxythiophene | Sigma-Aldrich | 483028 | Purified by vacuum distillation |
| 3-(4,5-Dimethylthiazol-2-yl)-2,5-Diphenyltetrazolium Bromide (MTT) 98% | Alfa Aesar | L11939 | |
| 505 Sonic Dismembrator | Fisher Scientific™ | FB505110 | 1/8 “ tip and rated at 500 watts |
| 808 nm laser diode | ThorLabs | L808P1WJ | Rated at 1 W |
| Acetonitrile anhydrous 99% | Acros | 61022-0010 | |
| Avanti J-26 XPI | Beckman Coulter | 393127 | |
| Bromohexane 98% | MP Biomedicals | 202323 | |
| Dialysis (100,000) MWCO | SpectrumLabs | G235071 | |
| Dimethyl sulfoxide 99% (DMSO) | BDH | BDH1115 | |
| Dimethylformamide anhydrous (DMF) 99% | Acros | 326870010 | |
| Dodecyl benzenesulfonate (DBSA) | TCI | D0989 | |
| Dulbecco’s modified eagle medium (DMEM) | Corning | 10-013 CV | |
| EMS 150 TES sputter coater | Electron Microscopy Sciences | ||
| Ethanol (EtOH) 100% | BDH | BDH1156 | |
| ethyl 4-bromobutyrate (98%) | Acros | 173551000 | |
| Ethyl acetate 99% | Fisher | UN1173 | |
| Fetal bovine serum (FBS) | Corning | 35-010-CV | |
| Helios NanoLab 400 | FEI | ||
| Hexane | Fisher | H306-4 | |
| Hydrochloric acid (HCl) | Fisher | A142-212 | |
| Hydroquinone 99.5% | Acros | 120915000 | |
| Hydrozine anhydrous 98% | Sigma-Aldrich | 215155 | |
| Indium tin oxide (ITO) coated galss | Delta Technologies | CG-41IN-CUV | 4-8 Ω/sq |
| Iron chloride 97% FeCl3 | Sigma-Aldrich | 157740 | |
| Magnesium sulfate (MgSO4) | Fisher | 593295 | Dried at 100 oC |
| SKOV-3 | ATCC | HTB-26 | |
| Methanol | BDH | BHD1135 | |
| n-Butlithium (2.5 M) | Sigma-Aldrich | 230707 | Pyrophoric |
| Poly(styrenesulfonate-co-malic acid) (PSS-co-MA) 20,000 MW | Sigma-Aldrich | 434566 | |
| Potassium carbonate | Sigma-Aldrich | 209619 | Dried at 100 oC |
| Potassium hydroxide | Alfa Aesar | A18854 | |
| Potassium iodide | Fisher | P410-100 | |
| RO-5 stirplate | IKA-Werke | ||
| SC4000 IR camera | FLIR | ||
| Synergy H4 Hybrid Reader | Biotek | ||
| Tetrabutylammonium perchlorate (TBAP) 99% | Sigma-Aldrich | 3579274 | Purified by recrystallization in ethyl acetate |
| Tetrahydrofuran anhydrous (THF) 99% | Sigma-Aldrich | 401757 | |
| tetrakis(triphenylphosphine) palladium(0) |
Sigma-Aldrich | 216666 | Moisture sensitive |
| Thermomixer | Eppendorf | ||
| USB potentiostat/galvanostat | WaveNow | AFTP1 | |
| Zetasizer Nano Zs | Malvern | Optical Arrangment 175o | |
| Zinc chloride (1 M) ZnCl2 | Acros | 370057000 |
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