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Charge-conversional and reduction-sensitive poly(vinyl alcohol) nanogels for enhanced cell uptake and efficient intracellular doxorubicin release.
J Control Release. 2015 May 10; 205:15-24.JC

Abstract

Charge-conversional and reduction-sensitive polyvinyl alcohol (PVA) nanogels were developed for efficient cancer treatment by enhanced cell uptake and intracellular triggered doxorubicin (DOX) release. These PVA nanogels were prepared in a straightforward manner by inverse nanoprecipitation via "click" reaction with an average diameter of 118nm. The introduction of COOH into the PVA nanogels efficiently improved the DOX encapsulation due to the electrostatic interaction. The in vitro release result showed that the decrease of electrostatic interaction between COOH and DOX under a mimicking endosomal pH, in combination with the cleavage of the intervening disulfide bonds in response to a high glutathione (GSH) concentration led to a fast and complete release of DOX. Furthermore, confocal laser scanning microscopy (CLSM) revealed that the ultra pH-sensitive terminal groups allowed nanogels to reverse their surface charge from negative to positive under a tumor extracellular pH (6.5-6.8) which facilitated cell internalization. MTT assays and real time cell analysis (RTCA) showed that these DOX-loaded charge-conversional and reducible PVA nanogels had much better cell toxicity than DOX-loaded non-charge-conversional or reduction-insensitive PVA nanogels following 48h of incubation. These novel charge-conversional and stimuli-responsive PVA nanogels are highly promising for targeted intracellular anticancer drug release.

Authors+Show Affiliations

Institute of Chemistry and Biochemistry, Freie Universität Berlin, Takustrasse 3, Berlin 14195, Germany.Institute of Chemistry and Biochemistry, Freie Universität Berlin, Takustrasse 3, Berlin 14195, Germany.Research Center of Electron Microscopy, Institute of Chemistry and Biochemistry, Freie Universität Berlin, Fabeckstrasse 36a, Berlin 14195, Germany.Institute of Chemistry and Biochemistry, Freie Universität Berlin, Takustrasse 3, Berlin 14195, Germany. Electronic address: haag@chemie.fu-berlin.de.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

25445693

Citation

Chen, Wei, et al. "Charge-conversional and Reduction-sensitive Poly(vinyl Alcohol) Nanogels for Enhanced Cell Uptake and Efficient Intracellular Doxorubicin Release." Journal of Controlled Release : Official Journal of the Controlled Release Society, vol. 205, 2015, pp. 15-24.
Chen W, Achazi K, Schade B, et al. Charge-conversional and reduction-sensitive poly(vinyl alcohol) nanogels for enhanced cell uptake and efficient intracellular doxorubicin release. J Control Release. 2015;205:15-24.
Chen, W., Achazi, K., Schade, B., & Haag, R. (2015). Charge-conversional and reduction-sensitive poly(vinyl alcohol) nanogels for enhanced cell uptake and efficient intracellular doxorubicin release. Journal of Controlled Release : Official Journal of the Controlled Release Society, 205, 15-24. https://doi.org/10.1016/j.jconrel.2014.11.012
Chen W, et al. Charge-conversional and Reduction-sensitive Poly(vinyl Alcohol) Nanogels for Enhanced Cell Uptake and Efficient Intracellular Doxorubicin Release. J Control Release. 2015 May 10;205:15-24. PubMed PMID: 25445693.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Charge-conversional and reduction-sensitive poly(vinyl alcohol) nanogels for enhanced cell uptake and efficient intracellular doxorubicin release. AU - Chen,Wei, AU - Achazi,Katharina, AU - Schade,Boris, AU - Haag,Rainer, Y1 - 2014/11/20/ PY - 2014/10/02/received PY - 2014/11/05/revised PY - 2014/11/16/accepted PY - 2014/12/3/entrez PY - 2014/12/3/pubmed PY - 2016/1/13/medline KW - Charge-conversion KW - Drug delivery KW - Inverse nanoprecipitation KW - PVA nanogel KW - Stimuli-responsive SP - 15 EP - 24 JF - Journal of controlled release : official journal of the Controlled Release Society JO - J Control Release VL - 205 N2 - Charge-conversional and reduction-sensitive polyvinyl alcohol (PVA) nanogels were developed for efficient cancer treatment by enhanced cell uptake and intracellular triggered doxorubicin (DOX) release. These PVA nanogels were prepared in a straightforward manner by inverse nanoprecipitation via "click" reaction with an average diameter of 118nm. The introduction of COOH into the PVA nanogels efficiently improved the DOX encapsulation due to the electrostatic interaction. The in vitro release result showed that the decrease of electrostatic interaction between COOH and DOX under a mimicking endosomal pH, in combination with the cleavage of the intervening disulfide bonds in response to a high glutathione (GSH) concentration led to a fast and complete release of DOX. Furthermore, confocal laser scanning microscopy (CLSM) revealed that the ultra pH-sensitive terminal groups allowed nanogels to reverse their surface charge from negative to positive under a tumor extracellular pH (6.5-6.8) which facilitated cell internalization. MTT assays and real time cell analysis (RTCA) showed that these DOX-loaded charge-conversional and reducible PVA nanogels had much better cell toxicity than DOX-loaded non-charge-conversional or reduction-insensitive PVA nanogels following 48h of incubation. These novel charge-conversional and stimuli-responsive PVA nanogels are highly promising for targeted intracellular anticancer drug release. SN - 1873-4995 UR - https://www.unboundmedicine.com/medline/citation/25445693/Charge_conversional_and_reduction_sensitive_poly_vinyl_alcohol__nanogels_for_enhanced_cell_uptake_and_efficient_intracellular_doxorubicin_release_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0168-3659(14)00749-4 DB - PRIME DP - Unbound Medicine ER -