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Poly(ethylene glycol)-sheddable reduction-sensitive polyurethane micelles for triggered intracellular drug delivery for osteosarcoma treatment

BACKGROUND: The survival rate of osteosarcoma therapy still lags behind overall cancer therapies due to the intrinsic or acquired drug resistance. Developing novel drug delivery systems that may overcome drug resistance would greatly facilitate osteosarcoma therapy. METHODS: Poly(ethylene glycol) (P...

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Autores principales: Yang, Zhengjie, Guo, Qianping, Cai, Yan, Zhu, Xuesong, Zhu, Caihong, Li, Yuling, Li, Bin
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Chinese Speaking Orthopaedic Society 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7029171/
https://www.ncbi.nlm.nih.gov/pubmed/32099805
http://dx.doi.org/10.1016/j.jot.2019.11.001
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author Yang, Zhengjie
Guo, Qianping
Cai, Yan
Zhu, Xuesong
Zhu, Caihong
Li, Yuling
Li, Bin
author_facet Yang, Zhengjie
Guo, Qianping
Cai, Yan
Zhu, Xuesong
Zhu, Caihong
Li, Yuling
Li, Bin
author_sort Yang, Zhengjie
collection PubMed
description BACKGROUND: The survival rate of osteosarcoma therapy still lags behind overall cancer therapies due to the intrinsic or acquired drug resistance. Developing novel drug delivery systems that may overcome drug resistance would greatly facilitate osteosarcoma therapy. METHODS: Poly(ethylene glycol) (PEG)-sheddable reduction-sensitive polyurethane (SS-PU-SS-PEG) was synthesized using a disulfide-containing polycaprolactone diol as the hydrophobic block and a cystamine-functionalized PEG as the hydrophilic block. SS-PU-SS-PEG micelles were then prepared to load the anti-tumor drug Doxorubicin (DOX) in order to achieve triggered intracellular drug delivery to improve the efficacy of osteosarcoma therapy. RESULTS: When DOX was used as a model drug, the drug-loaded SS-PU-SS-PEG micelles were about 82∼94 nm in diameter and exhibited good stability in phosphate buffer saline (PBS). The micelles could release about 80% DOX in a quantitative fashion within 5 hours under a reductive environment. The intracellular drug release of DOX-loaded SS-PU-SS-PEG micelles increased upon incubation with Saos-2 cells in vitro. The micelles had good biocompatibility. In vitro, DOX-loaded SS-PU-SS-PEG micelles showed significant antitumor activity toward Saos-2 cells, which was close to that of free DOX. In vivo, DOX-loaded SS-PU-SS-PEG micelles exhibited better antitumor activity than free DOX. CONCLUSION: Findings from this study suggest that the SS-PU-SS-PEG micelles could achieve well-controlled triggered drug release in a reduction environment and could therefore improve the antitumor efficacy of osteosarcoma therapies. TRANSLATION POTENTIAL OF THIS ARTICLE: In this study we developed PEG-sheddable reduction-sensitive polyurethane micelles (SS-PU-SS-PEG), which were able to achieve well-controlled triggered release of anti-tumor drug Doxorubicin (DOX) in an intracellular reduction environment. DOX-loaded SS-PU-SS-PEG micelles markedly improved the antitumor efficacy in a Saos-2 cells-bearing xenograft tumor model. Therefore, such micelles might be used as a novel drug delivery system for osteosarcoma treatment.
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spelling pubmed-70291712020-02-25 Poly(ethylene glycol)-sheddable reduction-sensitive polyurethane micelles for triggered intracellular drug delivery for osteosarcoma treatment Yang, Zhengjie Guo, Qianping Cai, Yan Zhu, Xuesong Zhu, Caihong Li, Yuling Li, Bin J Orthop Translat Original Article BACKGROUND: The survival rate of osteosarcoma therapy still lags behind overall cancer therapies due to the intrinsic or acquired drug resistance. Developing novel drug delivery systems that may overcome drug resistance would greatly facilitate osteosarcoma therapy. METHODS: Poly(ethylene glycol) (PEG)-sheddable reduction-sensitive polyurethane (SS-PU-SS-PEG) was synthesized using a disulfide-containing polycaprolactone diol as the hydrophobic block and a cystamine-functionalized PEG as the hydrophilic block. SS-PU-SS-PEG micelles were then prepared to load the anti-tumor drug Doxorubicin (DOX) in order to achieve triggered intracellular drug delivery to improve the efficacy of osteosarcoma therapy. RESULTS: When DOX was used as a model drug, the drug-loaded SS-PU-SS-PEG micelles were about 82∼94 nm in diameter and exhibited good stability in phosphate buffer saline (PBS). The micelles could release about 80% DOX in a quantitative fashion within 5 hours under a reductive environment. The intracellular drug release of DOX-loaded SS-PU-SS-PEG micelles increased upon incubation with Saos-2 cells in vitro. The micelles had good biocompatibility. In vitro, DOX-loaded SS-PU-SS-PEG micelles showed significant antitumor activity toward Saos-2 cells, which was close to that of free DOX. In vivo, DOX-loaded SS-PU-SS-PEG micelles exhibited better antitumor activity than free DOX. CONCLUSION: Findings from this study suggest that the SS-PU-SS-PEG micelles could achieve well-controlled triggered drug release in a reduction environment and could therefore improve the antitumor efficacy of osteosarcoma therapies. TRANSLATION POTENTIAL OF THIS ARTICLE: In this study we developed PEG-sheddable reduction-sensitive polyurethane micelles (SS-PU-SS-PEG), which were able to achieve well-controlled triggered release of anti-tumor drug Doxorubicin (DOX) in an intracellular reduction environment. DOX-loaded SS-PU-SS-PEG micelles markedly improved the antitumor efficacy in a Saos-2 cells-bearing xenograft tumor model. Therefore, such micelles might be used as a novel drug delivery system for osteosarcoma treatment. Chinese Speaking Orthopaedic Society 2019-12-06 /pmc/articles/PMC7029171/ /pubmed/32099805 http://dx.doi.org/10.1016/j.jot.2019.11.001 Text en © 2019 The Author(s) http://creativecommons.org/licenses/by-nc-nd/4.0/ This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
spellingShingle Original Article
Yang, Zhengjie
Guo, Qianping
Cai, Yan
Zhu, Xuesong
Zhu, Caihong
Li, Yuling
Li, Bin
Poly(ethylene glycol)-sheddable reduction-sensitive polyurethane micelles for triggered intracellular drug delivery for osteosarcoma treatment
title Poly(ethylene glycol)-sheddable reduction-sensitive polyurethane micelles for triggered intracellular drug delivery for osteosarcoma treatment
title_full Poly(ethylene glycol)-sheddable reduction-sensitive polyurethane micelles for triggered intracellular drug delivery for osteosarcoma treatment
title_fullStr Poly(ethylene glycol)-sheddable reduction-sensitive polyurethane micelles for triggered intracellular drug delivery for osteosarcoma treatment
title_full_unstemmed Poly(ethylene glycol)-sheddable reduction-sensitive polyurethane micelles for triggered intracellular drug delivery for osteosarcoma treatment
title_short Poly(ethylene glycol)-sheddable reduction-sensitive polyurethane micelles for triggered intracellular drug delivery for osteosarcoma treatment
title_sort poly(ethylene glycol)-sheddable reduction-sensitive polyurethane micelles for triggered intracellular drug delivery for osteosarcoma treatment
topic Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7029171/
https://www.ncbi.nlm.nih.gov/pubmed/32099805
http://dx.doi.org/10.1016/j.jot.2019.11.001
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