Dual pH and ultrasound responsive nanoparticles with pH triggered surface charge-conversional properties

T. Yildirim, I. Yildirim, R. Yañez-Macias, S. Stumpf, C. Fritzsche, S. Hoeppener, C. Guerrero-Sanchez, S. Schubert, U.S. Schubert

Research output: Contribution to journalArticle

Abstract

A series of dual pH- and ultrasound responsive statistical copolymers were synthesized via the reversible addition–fragmentation chain transfer (RAFT) polymerization of 3,4-dihydro-2H-pyran (DHP) protected HEMA 2-((tetrahydro-2H-pyran-2-yl)oxy)ethyl methacrylate (THP-HEMA) and 2-(dimethylamino)ethyl methacrylate (DMAEMA). The RAFT-controlled nature of the (co)polymerizations was verified by detailed kinetic studies. The chemical structure and the co-monomer composition of the copolymers were confirmed by 1H NMR spectroscopy. The number-average molar mass values (Mn) and dispersities (ĐM = Mw/Mn) of the copolymers were estimated by size exclusion chromatography (SEC). The thermal properties of the (co)polymers were analyzed by means of thermogravimetric analysis (TGA) and differential scanning calorimetry (DSC). Additionally, the DMAEMA moieties of the copolymers were quaternized with an excess of methyl iodide. The synthesized polymers self-assemble into nanoparticles in aqueous media via the nanoprecipitation method and were characterized by dynamic light scattering (DLS) and transmission electron microscopy (TEM). Zeta potential measurements revealed that all DMAEMA containing nanoparticles undergo a surface charge conversion from positive to negative at slightly acidic pH values. However, quaternized DMAEMA nanoparticles possess pH independent positive surface charges. At acidic pH values, the nanoparticles disassemble and dissolve in water due to the protonation of the DMAEMA moieties and/or due to the acidic hydrolysis of the THP-HEMA groups. It was found that the surface charge and the stability of the nanoparticles were greatly affected by the DMAEMA content of the polymers, meaning that the isoelectric point (IEP), at which the charge is reversed and the pH value at which the disassembly occurs, increased with the higher DMAEMA content in the copolymer. Moreover, it was proven that the ionization of the carboxyl RAFT end-group of the polymers enhanced the anionic character and the stability of the nanoparticles at neutral pH values. DLS and scanning electron microscopy (SEM) measurements revealed that these nanoparticles can be further disrupted by ultrasound exposure. Nile Red was encapsulated into nanoparticles as a model hydrophobic drug. The release profile of the Nile Red was significantly accelerated in acidic media or under ultrasound exposure. The cytotoxicity assay results showed that negatively charged nanoparticles are non-toxic and biocompatible, whereas positively charged nanoparticles are extremely toxic to L929 cells.
Original languageEnglish
Pages (from-to)1328-1340
JournalPolymer Chemistry
Volume8
DOIs
Publication statusPublished - 16 Jan 2017

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Surface charge
Nanoparticles
Methacrylates
Ultrasonics
Copolymers
Polymers
Dynamic light scattering
Polymerization
Pyrans
Size exclusion chromatography
Molar mass
Poisons
Protonation
Differential Scanning Calorimetry
Isoelectric Point
Zeta potential
Cytotoxicity
Light transmission
Transmission Electron Microscopy
Electron Scanning Microscopy

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Yildirim, T., Yildirim, I., Yañez-Macias, R., Stumpf, S., Fritzsche, C., Hoeppener, S., ... Schubert, U. S. (2017). Dual pH and ultrasound responsive nanoparticles with pH triggered surface charge-conversional properties. Polymer Chemistry, 8, 1328-1340. https://doi.org/10.1039/c6py01927g
Yildirim, T. ; Yildirim, I. ; Yañez-Macias, R. ; Stumpf, S. ; Fritzsche, C. ; Hoeppener, S. ; Guerrero-Sanchez, C. ; Schubert, S. ; Schubert, U.S. / Dual pH and ultrasound responsive nanoparticles with pH triggered surface charge-conversional properties. In: Polymer Chemistry. 2017 ; Vol. 8. pp. 1328-1340.
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Yildirim, T, Yildirim, I, Yañez-Macias, R, Stumpf, S, Fritzsche, C, Hoeppener, S, Guerrero-Sanchez, C, Schubert, S & Schubert, US 2017, 'Dual pH and ultrasound responsive nanoparticles with pH triggered surface charge-conversional properties', Polymer Chemistry, vol. 8, pp. 1328-1340. https://doi.org/10.1039/c6py01927g

Dual pH and ultrasound responsive nanoparticles with pH triggered surface charge-conversional properties. / Yildirim, T.; Yildirim, I.; Yañez-Macias, R.; Stumpf, S.; Fritzsche, C.; Hoeppener, S.; Guerrero-Sanchez, C.; Schubert, S.; Schubert, U.S.

In: Polymer Chemistry, Vol. 8, 16.01.2017, p. 1328-1340.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Dual pH and ultrasound responsive nanoparticles with pH triggered surface charge-conversional properties

AU - Yildirim, T.

AU - Yildirim, I.

AU - Yañez-Macias, R.

AU - Stumpf, S.

AU - Fritzsche, C.

AU - Hoeppener, S.

AU - Guerrero-Sanchez, C.

AU - Schubert, S.

AU - Schubert, U.S.

PY - 2017/1/16

Y1 - 2017/1/16

N2 - A series of dual pH- and ultrasound responsive statistical copolymers were synthesized via the reversible addition–fragmentation chain transfer (RAFT) polymerization of 3,4-dihydro-2H-pyran (DHP) protected HEMA 2-((tetrahydro-2H-pyran-2-yl)oxy)ethyl methacrylate (THP-HEMA) and 2-(dimethylamino)ethyl methacrylate (DMAEMA). The RAFT-controlled nature of the (co)polymerizations was verified by detailed kinetic studies. The chemical structure and the co-monomer composition of the copolymers were confirmed by 1H NMR spectroscopy. The number-average molar mass values (Mn) and dispersities (ĐM = Mw/Mn) of the copolymers were estimated by size exclusion chromatography (SEC). The thermal properties of the (co)polymers were analyzed by means of thermogravimetric analysis (TGA) and differential scanning calorimetry (DSC). Additionally, the DMAEMA moieties of the copolymers were quaternized with an excess of methyl iodide. The synthesized polymers self-assemble into nanoparticles in aqueous media via the nanoprecipitation method and were characterized by dynamic light scattering (DLS) and transmission electron microscopy (TEM). Zeta potential measurements revealed that all DMAEMA containing nanoparticles undergo a surface charge conversion from positive to negative at slightly acidic pH values. However, quaternized DMAEMA nanoparticles possess pH independent positive surface charges. At acidic pH values, the nanoparticles disassemble and dissolve in water due to the protonation of the DMAEMA moieties and/or due to the acidic hydrolysis of the THP-HEMA groups. It was found that the surface charge and the stability of the nanoparticles were greatly affected by the DMAEMA content of the polymers, meaning that the isoelectric point (IEP), at which the charge is reversed and the pH value at which the disassembly occurs, increased with the higher DMAEMA content in the copolymer. Moreover, it was proven that the ionization of the carboxyl RAFT end-group of the polymers enhanced the anionic character and the stability of the nanoparticles at neutral pH values. DLS and scanning electron microscopy (SEM) measurements revealed that these nanoparticles can be further disrupted by ultrasound exposure. Nile Red was encapsulated into nanoparticles as a model hydrophobic drug. The release profile of the Nile Red was significantly accelerated in acidic media or under ultrasound exposure. The cytotoxicity assay results showed that negatively charged nanoparticles are non-toxic and biocompatible, whereas positively charged nanoparticles are extremely toxic to L929 cells.

AB - A series of dual pH- and ultrasound responsive statistical copolymers were synthesized via the reversible addition–fragmentation chain transfer (RAFT) polymerization of 3,4-dihydro-2H-pyran (DHP) protected HEMA 2-((tetrahydro-2H-pyran-2-yl)oxy)ethyl methacrylate (THP-HEMA) and 2-(dimethylamino)ethyl methacrylate (DMAEMA). The RAFT-controlled nature of the (co)polymerizations was verified by detailed kinetic studies. The chemical structure and the co-monomer composition of the copolymers were confirmed by 1H NMR spectroscopy. The number-average molar mass values (Mn) and dispersities (ĐM = Mw/Mn) of the copolymers were estimated by size exclusion chromatography (SEC). The thermal properties of the (co)polymers were analyzed by means of thermogravimetric analysis (TGA) and differential scanning calorimetry (DSC). Additionally, the DMAEMA moieties of the copolymers were quaternized with an excess of methyl iodide. The synthesized polymers self-assemble into nanoparticles in aqueous media via the nanoprecipitation method and were characterized by dynamic light scattering (DLS) and transmission electron microscopy (TEM). Zeta potential measurements revealed that all DMAEMA containing nanoparticles undergo a surface charge conversion from positive to negative at slightly acidic pH values. However, quaternized DMAEMA nanoparticles possess pH independent positive surface charges. At acidic pH values, the nanoparticles disassemble and dissolve in water due to the protonation of the DMAEMA moieties and/or due to the acidic hydrolysis of the THP-HEMA groups. It was found that the surface charge and the stability of the nanoparticles were greatly affected by the DMAEMA content of the polymers, meaning that the isoelectric point (IEP), at which the charge is reversed and the pH value at which the disassembly occurs, increased with the higher DMAEMA content in the copolymer. Moreover, it was proven that the ionization of the carboxyl RAFT end-group of the polymers enhanced the anionic character and the stability of the nanoparticles at neutral pH values. DLS and scanning electron microscopy (SEM) measurements revealed that these nanoparticles can be further disrupted by ultrasound exposure. Nile Red was encapsulated into nanoparticles as a model hydrophobic drug. The release profile of the Nile Red was significantly accelerated in acidic media or under ultrasound exposure. The cytotoxicity assay results showed that negatively charged nanoparticles are non-toxic and biocompatible, whereas positively charged nanoparticles are extremely toxic to L929 cells.

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