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pH-responsive PEGylated doxorubicin for efficient cancer chemotherapy
Abstracts / Journal of Controlled Release 213 (2015) e8–e152
would disassociate in the cancer cells, which resulted in the rapid release of PTX and TPGS active ingredient. P-glycoprotein (P-gp) could be blocked by TPGS and intracellular PTX concentration was improved. On the other hand, the quick and large amount of released NO would induce the apoptosis of tumor cells. Thanks to the synergistic effect of PTX and NO, significant cell cytotoxicity and apoptosis was observed compared with TPGS-S-S–PTX or TNO3 alone. Moreover, the NO gas was capable of dilating the blood vessels and reducing the interstitial pressure in tumor tissue [2]. This may be resulted an enhanced accumulation and perfusion of the micelles as well as a deeper tumor penetration. At last, enhanced antitumor activity was achieved on S180 tumor bearing mice. In summary, this novel multifunctional mixed micelle provides a new way in cancer treatment.
e149
antitumor efficacy and decreased side effects, indicating that PEGylated antitumor drug, CAD–PEG–CAD, is a promising and efficient prodrug for cancer chemotherapy.
Keywords: redox-sensitive, TPGS, Paclitaxel, Nitric oxide, Micelle Acknowledgements This work was supported by the National Basic Research Program of China (973 Program, 2012CB932501) and the National Natural Science Foundation of China (21204024 and 81373360). References [1] J.R. Sang, Y.C. Chen, Y. Tao, Nitric oxide inhibits gastric cancer cell growth through the modulation of the Akt pathway, Mol. Med. Rep. 4 (2011) 1163–1167. [2] H. Yasuda, Solid tumor physiology and hypoxia-induced chemo/ radio-resistance: novel strategy for cancer therapy: nitric oxide donor as a therapeutic enhancer, Nitric Oxide 19 (2008) 205–216.
Scheme 1. CAD–PEG–CAD prodrug nanoparticle formation and intracellular targeting DOX release.
Keywords: cancer therapy, controlled release, doxorubicin, poly(ethylene glycol), pH-responsive Acknowledgments This work was financially supported by the National Natural Science Foundation of China (51303174, 51321062, 51233004 and 51390484).
doi:10.1016/j.jconrel.2015.05.251
pH-responsive PEGylated doxorubicin for efficient cancer chemotherapy Zhiyu Zhanga,*, Xueyuan Gub, Diankui Sunc,*, Jianxun Dingc, Qin Lib,*, Xiuli Zhuangc, Xuesi Chenc a Department of Orthopedics, 4th Affiliated Hospital of China Medical University, Shenyang 110032, China b Laboratory Center, 4th Affiliated Hospital of China Medical University, Shenyang 110032, China c Key Laboratory of Polymer Ecomaterials, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun 130022, China ⁎Corresponding authors. E-mail addresses: [email protected] (Z. Zhang), [email protected] (D. Sun), [email protected] (Q. Li). Poly(ethylene glycol) (PEG) with good biocompatibility and resistance to protein adsorption is the commonly used hydrophilic segment in nanocarriers for intravenous administration [1]. PEGmodified doxorubicin (DOX) has been a promising polymeric prodrug that exhibited improved DOX solubility, decreased side effects and enhanced efficacy [2]. In this work, acid-sensitive PEGylated DOX was designed and prepared for cancer inhibition. In detail, the cis-aconitic anhydride (CA) modified DOX (CAD) was synthesized through the ring-opening reaction of cis-aconitic anhydride initiated by the amino group of DOX, and then the obtained CAD was conjugated onto the terminal hydroxyl group of PEG, yielding pH-responsive CAD–PEG–CAD prodrug. As shown in Scheme 1, the prodrug self-assembled into spherical nanoparticles in aqueous solution, which exhibited enhanced accumulation in tumor tissue benefited from enhanced permeability and retention effect. Comparing to free DOX, CAD– PEG–CAD nanoparticles had acid-accelerated DOX release, enhanced
References [1] J.X. Ding, D. Li, X.L. Zhuang, X.S. Chen, Self-assemblies of pHactivatable PEGylated multi-arm poly(lactic acid-co-glycolic acid)-doxorubicin prodrugs with improved long-term antitumor efficacies, Macromol. Biosci. 13 (2013) 1300–1307. [2] P.F. Gou, W.W. Liu, W.W. Mao, J.B. Tang, Y.Q. Shen, M.H. Sui, Self-assembling doxorubicin prodrug forming nanoparticles for cancer chemotherapy: synthesis and anticancer study in vitro and in vivo, J. Mater. Chem. B 1 (2013) 284–292. doi:10.1016/j.jconrel.2015.05.252
Electrospun PLA/MWCNT composite nanofibers for combined chemo- and photothermal therapy with near-infrared radiation Zhiyun Zhang, Shi Liu, Xiabin Jing, Yubin Huang* State Key Laboratory of polymer Physics and Chemistry, Changchun Institute of Applied Chemistry, Chinese Academy of Science, Changchun 130022, China ⁎Corresponding author. E-mail addresses: [email protected] (Z. Zhang), [email protected] (Y. Huang). Current clinical therapy investigation has shown that a combination of chemo- and thermotherapy could enhance anticancer efficacy. Among the drug delivery systems, electrospun nanofibers have shown particularly good potential for drug delivery due to their high area to volume ratio and porosity [1]. Multi-walled carbon nanotubes (MWCNTs), which have excellent biocompatibility, can convert near-infrared (NIR) laser irradiation into heat. Different drugs can be loaded into tubes of MWCNTs which have recently attracted attention to consider these tubes as potential drug delivery vehicles [2].
would disassociate in the cancer cells, which resulted in the rapid release of PTX and TPGS active ingredient. P-glycoprotein (P-gp) could be blocked by TPGS and intracellular PTX concentration was improved. On the other hand, the quick and large amount of released NO would induce the apoptosis of tumor cells. Thanks to the synergistic effect of PTX and NO, significant cell cytotoxicity and apoptosis was observed compared with TPGS-S-S–PTX or TNO3 alone. Moreover, the NO gas was capable of dilating the blood vessels and reducing the interstitial pressure in tumor tissue [2]. This may be resulted an enhanced accumulation and perfusion of the micelles as well as a deeper tumor penetration. At last, enhanced antitumor activity was achieved on S180 tumor bearing mice. In summary, this novel multifunctional mixed micelle provides a new way in cancer treatment.
e149
antitumor efficacy and decreased side effects, indicating that PEGylated antitumor drug, CAD–PEG–CAD, is a promising and efficient prodrug for cancer chemotherapy.
Keywords: redox-sensitive, TPGS, Paclitaxel, Nitric oxide, Micelle Acknowledgements This work was supported by the National Basic Research Program of China (973 Program, 2012CB932501) and the National Natural Science Foundation of China (21204024 and 81373360). References [1] J.R. Sang, Y.C. Chen, Y. Tao, Nitric oxide inhibits gastric cancer cell growth through the modulation of the Akt pathway, Mol. Med. Rep. 4 (2011) 1163–1167. [2] H. Yasuda, Solid tumor physiology and hypoxia-induced chemo/ radio-resistance: novel strategy for cancer therapy: nitric oxide donor as a therapeutic enhancer, Nitric Oxide 19 (2008) 205–216.
Scheme 1. CAD–PEG–CAD prodrug nanoparticle formation and intracellular targeting DOX release.
Keywords: cancer therapy, controlled release, doxorubicin, poly(ethylene glycol), pH-responsive Acknowledgments This work was financially supported by the National Natural Science Foundation of China (51303174, 51321062, 51233004 and 51390484).
doi:10.1016/j.jconrel.2015.05.251
pH-responsive PEGylated doxorubicin for efficient cancer chemotherapy Zhiyu Zhanga,*, Xueyuan Gub, Diankui Sunc,*, Jianxun Dingc, Qin Lib,*, Xiuli Zhuangc, Xuesi Chenc a Department of Orthopedics, 4th Affiliated Hospital of China Medical University, Shenyang 110032, China b Laboratory Center, 4th Affiliated Hospital of China Medical University, Shenyang 110032, China c Key Laboratory of Polymer Ecomaterials, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun 130022, China ⁎Corresponding authors. E-mail addresses: [email protected] (Z. Zhang), [email protected] (D. Sun), [email protected] (Q. Li). Poly(ethylene glycol) (PEG) with good biocompatibility and resistance to protein adsorption is the commonly used hydrophilic segment in nanocarriers for intravenous administration [1]. PEGmodified doxorubicin (DOX) has been a promising polymeric prodrug that exhibited improved DOX solubility, decreased side effects and enhanced efficacy [2]. In this work, acid-sensitive PEGylated DOX was designed and prepared for cancer inhibition. In detail, the cis-aconitic anhydride (CA) modified DOX (CAD) was synthesized through the ring-opening reaction of cis-aconitic anhydride initiated by the amino group of DOX, and then the obtained CAD was conjugated onto the terminal hydroxyl group of PEG, yielding pH-responsive CAD–PEG–CAD prodrug. As shown in Scheme 1, the prodrug self-assembled into spherical nanoparticles in aqueous solution, which exhibited enhanced accumulation in tumor tissue benefited from enhanced permeability and retention effect. Comparing to free DOX, CAD– PEG–CAD nanoparticles had acid-accelerated DOX release, enhanced
References [1] J.X. Ding, D. Li, X.L. Zhuang, X.S. Chen, Self-assemblies of pHactivatable PEGylated multi-arm poly(lactic acid-co-glycolic acid)-doxorubicin prodrugs with improved long-term antitumor efficacies, Macromol. Biosci. 13 (2013) 1300–1307. [2] P.F. Gou, W.W. Liu, W.W. Mao, J.B. Tang, Y.Q. Shen, M.H. Sui, Self-assembling doxorubicin prodrug forming nanoparticles for cancer chemotherapy: synthesis and anticancer study in vitro and in vivo, J. Mater. Chem. B 1 (2013) 284–292. doi:10.1016/j.jconrel.2015.05.252
Electrospun PLA/MWCNT composite nanofibers for combined chemo- and photothermal therapy with near-infrared radiation Zhiyun Zhang, Shi Liu, Xiabin Jing, Yubin Huang* State Key Laboratory of polymer Physics and Chemistry, Changchun Institute of Applied Chemistry, Chinese Academy of Science, Changchun 130022, China ⁎Corresponding author. E-mail addresses: [email protected] (Z. Zhang), [email protected] (Y. Huang). Current clinical therapy investigation has shown that a combination of chemo- and thermotherapy could enhance anticancer efficacy. Among the drug delivery systems, electrospun nanofibers have shown particularly good potential for drug delivery due to their high area to volume ratio and porosity [1]. Multi-walled carbon nanotubes (MWCNTs), which have excellent biocompatibility, can convert near-infrared (NIR) laser irradiation into heat. Different drugs can be loaded into tubes of MWCNTs which have recently attracted attention to consider these tubes as potential drug delivery vehicles [2].