A NAG-Guided Nano-Delivery System for Redox- and pH-Triggered Intracellularly Sequential Drug Release in Cancer Cells
Yan Liang,1 Jing Zhang,1 Baocheng Tian,1 Zimei Wu,2 Darren Svirskis,2 Jingtian Han1 1School of Pharmacy, Binzhou Medical University, Yantai 264003, Shandong Province, People’s Republic of China; 2School of Pharmacy, Faculty of Medical and Health Sciences, The University of Auckland, Auckla...
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Dove Medical Press
2020
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oai:doaj.org-article:bd5230a93d2246858b09338261eb879c2021-12-02T09:56:22ZA NAG-Guided Nano-Delivery System for Redox- and pH-Triggered Intracellularly Sequential Drug Release in Cancer Cells1178-2013https://doaj.org/article/bd5230a93d2246858b09338261eb879c2020-02-01T00:00:00Zhttps://www.dovepress.com/a-nag-guided-nano-delivery-system-for-redox--and-ph-triggered-intracel-peer-reviewed-article-IJNhttps://doaj.org/toc/1178-2013Yan Liang,1 Jing Zhang,1 Baocheng Tian,1 Zimei Wu,2 Darren Svirskis,2 Jingtian Han1 1School of Pharmacy, Binzhou Medical University, Yantai 264003, Shandong Province, People’s Republic of China; 2School of Pharmacy, Faculty of Medical and Health Sciences, The University of Auckland, Auckland 1023, New ZealandCorrespondence: Jingtian HanSchool of Pharmacy, Binzhou Medical University, 346 Guanhai Road, Yantai 264003, People’s Republic of ChinaTel +86-535-6913317Fax +86-535-6913718Email hanjingtian002@163.comDarren SvirskisSchool of Pharmacy, University of Auckland, 85 Park Road, Grafton, Auckland, New ZealandTel +64-9-923 1158Email d.svirskis@auckland.ac.nzAim: Sequential treatment with paclitaxel (PTXL) and gemcitabine (GEM) is considered clinically beneficial for non-small-cell lung cancer. This study aimed to investigate the effectiveness of a nano-system capable of sequential release of PTXL and GEM within cancer cells.Methods: PTXL-ss-poly(6-O-methacryloyl-d-galactopyranose)-GEM (PTXL-ss-PMAGP-GEM) was designed by conjugating PMAGP with PTXL via disulfide bonds (-ss-), while GEM via succinic anhydride (PTXL:GEM=1:3). An amphiphilic block copolymer N-acetyl-d-glucosamine(NAG)-poly(styrene-alt-maleic anhydride)58-b-polystyrene130 acted as a targeting moiety and emulsifier in formation of nanostructures (NLCs).Results: The PTXL-ss-PMAGP-GEM/NAG NLCs (119.6 nm) provided a sequential in vitro release of, first PTXL (redox-triggered), then GEM (pH-triggered). The redox- and pH-sensitive NLCs readily distributed homogenously in the cytoplasm. NAG augmented the uptake of NLCs by the cancer cells and tumor accumulation. PTXL-ss-PMAGP-GEM/NAG NLCs exhibited synergistic cytotoxicity in vitro and strongest antitumor effects in tumor-bearing mice compared to NLCs lacking pH/redox sensitivities or free drug combination.Conclusion: This study demonstrated the abilities of PTXL-ss-PMAGP-GEM/NAG NLCs to achieve synergistic antitumor effect by targeted intracellularly sequential drug release.Keywords: sequential release, redox-sensitive, pH-sensitive, synergistic efficiency, combination drug delivery, gemcitabine, paclitaxelLiang YZhang JTian BWu ZSvirskis DHan JDove Medical Pressarticlesequential releaseredox-sensitiveph-sensitivesynergistic efficiencycombination drug deliverygemcitabinepaclitaxelMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol Volume 15, Pp 841-855 (2020) |
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EN |
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sequential release redox-sensitive ph-sensitive synergistic efficiency combination drug delivery gemcitabine paclitaxel Medicine (General) R5-920 |
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sequential release redox-sensitive ph-sensitive synergistic efficiency combination drug delivery gemcitabine paclitaxel Medicine (General) R5-920 Liang Y Zhang J Tian B Wu Z Svirskis D Han J A NAG-Guided Nano-Delivery System for Redox- and pH-Triggered Intracellularly Sequential Drug Release in Cancer Cells |
| description |
Yan Liang,1 Jing Zhang,1 Baocheng Tian,1 Zimei Wu,2 Darren Svirskis,2 Jingtian Han1 1School of Pharmacy, Binzhou Medical University, Yantai 264003, Shandong Province, People’s Republic of China; 2School of Pharmacy, Faculty of Medical and Health Sciences, The University of Auckland, Auckland 1023, New ZealandCorrespondence: Jingtian HanSchool of Pharmacy, Binzhou Medical University, 346 Guanhai Road, Yantai 264003, People’s Republic of ChinaTel +86-535-6913317Fax +86-535-6913718Email hanjingtian002@163.comDarren SvirskisSchool of Pharmacy, University of Auckland, 85 Park Road, Grafton, Auckland, New ZealandTel +64-9-923 1158Email d.svirskis@auckland.ac.nzAim: Sequential treatment with paclitaxel (PTXL) and gemcitabine (GEM) is considered clinically beneficial for non-small-cell lung cancer. This study aimed to investigate the effectiveness of a nano-system capable of sequential release of PTXL and GEM within cancer cells.Methods: PTXL-ss-poly(6-O-methacryloyl-d-galactopyranose)-GEM (PTXL-ss-PMAGP-GEM) was designed by conjugating PMAGP with PTXL via disulfide bonds (-ss-), while GEM via succinic anhydride (PTXL:GEM=1:3). An amphiphilic block copolymer N-acetyl-d-glucosamine(NAG)-poly(styrene-alt-maleic anhydride)58-b-polystyrene130 acted as a targeting moiety and emulsifier in formation of nanostructures (NLCs).Results: The PTXL-ss-PMAGP-GEM/NAG NLCs (119.6 nm) provided a sequential in vitro release of, first PTXL (redox-triggered), then GEM (pH-triggered). The redox- and pH-sensitive NLCs readily distributed homogenously in the cytoplasm. NAG augmented the uptake of NLCs by the cancer cells and tumor accumulation. PTXL-ss-PMAGP-GEM/NAG NLCs exhibited synergistic cytotoxicity in vitro and strongest antitumor effects in tumor-bearing mice compared to NLCs lacking pH/redox sensitivities or free drug combination.Conclusion: This study demonstrated the abilities of PTXL-ss-PMAGP-GEM/NAG NLCs to achieve synergistic antitumor effect by targeted intracellularly sequential drug release.Keywords: sequential release, redox-sensitive, pH-sensitive, synergistic efficiency, combination drug delivery, gemcitabine, paclitaxel |
| format |
article |
| author |
Liang Y Zhang J Tian B Wu Z Svirskis D Han J |
| author_facet |
Liang Y Zhang J Tian B Wu Z Svirskis D Han J |
| author_sort |
Liang Y |
| title |
A NAG-Guided Nano-Delivery System for Redox- and pH-Triggered Intracellularly Sequential Drug Release in Cancer Cells |
| title_short |
A NAG-Guided Nano-Delivery System for Redox- and pH-Triggered Intracellularly Sequential Drug Release in Cancer Cells |
| title_full |
A NAG-Guided Nano-Delivery System for Redox- and pH-Triggered Intracellularly Sequential Drug Release in Cancer Cells |
| title_fullStr |
A NAG-Guided Nano-Delivery System for Redox- and pH-Triggered Intracellularly Sequential Drug Release in Cancer Cells |
| title_full_unstemmed |
A NAG-Guided Nano-Delivery System for Redox- and pH-Triggered Intracellularly Sequential Drug Release in Cancer Cells |
| title_sort |
nag-guided nano-delivery system for redox- and ph-triggered intracellularly sequential drug release in cancer cells |
| publisher |
Dove Medical Press |
| publishDate |
2020 |
| url |
https://doaj.org/article/bd5230a93d2246858b09338261eb879c |
| work_keys_str_mv |
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