A NAG-Guided Nano-Delivery System for Redox- and pH-Triggered Intracellularly Sequential Drug Release in Cancer Cells

International Journal of Nanomedicine

关键词: sequential release;    redox-sensitive;    ph-sensitive;    synergistic efficiency;    combination drug delivery;    gemcitabine;    paclitaxel;   

DOI  :  

来源: DOAJ

【 摘 要 】

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 [phone]Fax [phone]Email [e-mail] SvirskisSchool of Pharmacy, University of Auckland, 85 Park Road, Grafton, Auckland, New ZealandTel [phone]Email [e-mail]: 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

【 授权许可】

Unknown