- Email: [email protected]
Synergy of photodynamic therapy and chemotherapy with light-triggered drug release
Abstracts / Journal of Controlled Release 259 (2017) e5–e195
studied by confocal laser scanning microscopy. Furthermore, the in vivo imaging results proved the high tumor targeting efficiency of DVS-TSLs under hyperthermia. The therapeutic efficacy revealed that DVS-TSLs could significantly increase drug efficacy and decrease system toxicity. Therefore, the DVS-TSLs may serve as a promising system for temperature triggered cancer treatment. Keywords: doxorubicin, vincristine, salinomycin, cancer stem cells, thermosensitive liposome References [1] S. Gangopadhyay, A. Nandy, P. Hor, A. Mukhopadhyay. Breast cancer stem cells: a novel therapeutic target, Clin. Breast Cancer 13 (2013) 7-15. [2] K. Chatterjee, J. Zhang, N. Honbo, U. Simonis, R. Shaw, J.S. Karliner. Acute vincristine pretreatment protects adult mouse cardiac myocytes from oxidative stress, J. Mol. Cell. Cardiol. 43 (2007) 327-336. [3] J.P. May, M.J. Ernsting, E. Undzys, S.D. Li. Thermosensitive liposomes for the delivery of gemcitabine and oxaliplatin to tumors, Mol. Pharm. 10 (2013) 4499-4508.
doi:10.1016/j.jconrel.2017.03.206
Synergy of photodynamic therapy and chemotherapy with light-triggered drug release Mingzhou Yeb, Jianbin Tanga,⁎, Jianqing Gaob,⁎, Xiangrui Liua, Zhuxian Zhoua, Youqing Shena a Key Laboratory of Biomass Chemical Engineering of Ministry of Education and Center for Bionanoengineering, Department of Chemical and Biological Engineering, Zhejiang University, Hangzhou 310027, China b Institute of Pharmaceutics, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310027, China ⁎Corresponding authors. E-mail addresses: [email protected] (M. Ye), [email protected] (J. Tang), [email protected] (J. Gao)
e97
a reactive oxygen species (ROS) activatable prodrug BDox which derived from chemotherapy drug DOX and ROS-sensitive moiety boron ester. BDox revealed reduced cytotoxicity comparing with DOX, and it could be activated by ROS and recovered its cytotoxicity. The nanoparticle with diameter of 40 nm remained innocuous in the dark, whereas PPIX generated noxious ROS after light irradiation, and thereupon led to the activation and release of BDox (Fig. 1). By controlling the light irradiation, we could simply manipulate where and when the prodrug was activated, and avoided toxic and side effect to normal tissues. Moreover, the synergy between ROS and DOX could effectively overcome the drug resistance of cancer cells. The lighttriggered drug delivery system with excellent anticancer efficacy and reduced side effect could act as a promising system in developing nanomedicine. Keywords: light trigger, prodrug activation, ROS response, drug delivery, anticancer Acknowledgements This study was financially supported by the National Basic Research Program (2014CB931900), the National Nature Science Foundation of China (21174128, 51522304), and Fundamental Research Funds for the Central Universities. References [1] X. Wu, X. Sun, Z. Guo, J. Tang, Y. Shen, T.D. James, H. Tian, W.H. Zhu, In vivo and in situ tracking cancer chemotherapy by highly photostable NIR fluorescent theranostic prodrug, J. Am. Chem. Soc. 136 (2014) 3579-3588. [2] V. Biju, Chemical modifications and bioconjugate reactions of nanomaterials for sensing, imaging, drug delivery and therapy, Chem. Soc. Rev. 43 (2014) 744-764.
doi:10.1016/j.jconrel.2017.03.207
New treatment of Wilson´s disease Controlled drug release is critical for improving anticancer efficacy and reduing side effects of drug delivery systems [1]. Lighttriggered prodrug activation system, which integrates manipulable drug release and synergy of photodynamic therapy and chemotherapy, can increase anti-cancer efficacy and overcome the drug resistance of cancers [2]. In this work, we described a light-triggered drug delivery system that comprised photosensitizer protoporphyrin IX (PPIX), a biodegradable block copolymer poly(ethylene glycol)-poly(niacin) (PEG-PNC), which maintained the stealth and stability of the nanoparticle, as well as
Miroslav Vetrika,⁎, Jana Mattovab, Jan Kuckaa, Hana Mackovaa, Ondrej Sedlaceka, Pavla Pouckovab, Olivia Policianovaa, Jiri Brusa, Sebastian Eignerb, Ludek Sevcb, Petr Stepaneka, Martin Hrubya a Institute of Macromolecular Chemistry AS CR, v.v.i., Heyrovsky Sq. 2, 162 06, Prague, 6, Czech Republic b Institute of Biophysics and Informatics, First Faculty of Medicine, Charles University in Prague, Salmovska1, 120 00 Prague2, Czech Republic ⁎Corresponding author. E-mail address: [email protected] (M. Vetrik)
Fig. 1. Illustration of light-triggered drug delivery system.
Wilson’s disease is a genetic disorder causing excessive accumulation of copper in the body leading to toxic damage especially in the liver and in the nervous system. The current treatment is based on low-molecular weight copper chelators and zinc salts that have some burdensome side effects that arise as a consequence of absorption into the blood and organs after ingestion [1]. We design new biomaterials based on cellulose and crosslinked chitosan with covalently bounded copper chelator as potential drugs for the treatment of Wilson’s disease (Fig. 1). We proceeded from the fact that copper is absorbed into the body by the gastrointestinal tract. Therefore, new designed biopolymers should not be degradable in human digestive tract and should serve as copper scavengers. Our new proposed therapy utilizes specific copper chelating agent (8-hydroxyquinoline) that is covalently bound to carriers, cellulose or chitosan. New biocompatible carriers provide scavenging copper from gastrointestinal tract without organ deposition. Described compounds are eliminated through the feces after oral administration. We tested this idea in Wistar rats, which received radioactive 64Cu, with cellulose or chitosan with covalently bound 8-hydroxyquinoline. We
studied by confocal laser scanning microscopy. Furthermore, the in vivo imaging results proved the high tumor targeting efficiency of DVS-TSLs under hyperthermia. The therapeutic efficacy revealed that DVS-TSLs could significantly increase drug efficacy and decrease system toxicity. Therefore, the DVS-TSLs may serve as a promising system for temperature triggered cancer treatment. Keywords: doxorubicin, vincristine, salinomycin, cancer stem cells, thermosensitive liposome References [1] S. Gangopadhyay, A. Nandy, P. Hor, A. Mukhopadhyay. Breast cancer stem cells: a novel therapeutic target, Clin. Breast Cancer 13 (2013) 7-15. [2] K. Chatterjee, J. Zhang, N. Honbo, U. Simonis, R. Shaw, J.S. Karliner. Acute vincristine pretreatment protects adult mouse cardiac myocytes from oxidative stress, J. Mol. Cell. Cardiol. 43 (2007) 327-336. [3] J.P. May, M.J. Ernsting, E. Undzys, S.D. Li. Thermosensitive liposomes for the delivery of gemcitabine and oxaliplatin to tumors, Mol. Pharm. 10 (2013) 4499-4508.
doi:10.1016/j.jconrel.2017.03.206
Synergy of photodynamic therapy and chemotherapy with light-triggered drug release Mingzhou Yeb, Jianbin Tanga,⁎, Jianqing Gaob,⁎, Xiangrui Liua, Zhuxian Zhoua, Youqing Shena a Key Laboratory of Biomass Chemical Engineering of Ministry of Education and Center for Bionanoengineering, Department of Chemical and Biological Engineering, Zhejiang University, Hangzhou 310027, China b Institute of Pharmaceutics, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310027, China ⁎Corresponding authors. E-mail addresses: [email protected] (M. Ye), [email protected] (J. Tang), [email protected] (J. Gao)
e97
a reactive oxygen species (ROS) activatable prodrug BDox which derived from chemotherapy drug DOX and ROS-sensitive moiety boron ester. BDox revealed reduced cytotoxicity comparing with DOX, and it could be activated by ROS and recovered its cytotoxicity. The nanoparticle with diameter of 40 nm remained innocuous in the dark, whereas PPIX generated noxious ROS after light irradiation, and thereupon led to the activation and release of BDox (Fig. 1). By controlling the light irradiation, we could simply manipulate where and when the prodrug was activated, and avoided toxic and side effect to normal tissues. Moreover, the synergy between ROS and DOX could effectively overcome the drug resistance of cancer cells. The lighttriggered drug delivery system with excellent anticancer efficacy and reduced side effect could act as a promising system in developing nanomedicine. Keywords: light trigger, prodrug activation, ROS response, drug delivery, anticancer Acknowledgements This study was financially supported by the National Basic Research Program (2014CB931900), the National Nature Science Foundation of China (21174128, 51522304), and Fundamental Research Funds for the Central Universities. References [1] X. Wu, X. Sun, Z. Guo, J. Tang, Y. Shen, T.D. James, H. Tian, W.H. Zhu, In vivo and in situ tracking cancer chemotherapy by highly photostable NIR fluorescent theranostic prodrug, J. Am. Chem. Soc. 136 (2014) 3579-3588. [2] V. Biju, Chemical modifications and bioconjugate reactions of nanomaterials for sensing, imaging, drug delivery and therapy, Chem. Soc. Rev. 43 (2014) 744-764.
doi:10.1016/j.jconrel.2017.03.207
New treatment of Wilson´s disease Controlled drug release is critical for improving anticancer efficacy and reduing side effects of drug delivery systems [1]. Lighttriggered prodrug activation system, which integrates manipulable drug release and synergy of photodynamic therapy and chemotherapy, can increase anti-cancer efficacy and overcome the drug resistance of cancers [2]. In this work, we described a light-triggered drug delivery system that comprised photosensitizer protoporphyrin IX (PPIX), a biodegradable block copolymer poly(ethylene glycol)-poly(niacin) (PEG-PNC), which maintained the stealth and stability of the nanoparticle, as well as
Miroslav Vetrika,⁎, Jana Mattovab, Jan Kuckaa, Hana Mackovaa, Ondrej Sedlaceka, Pavla Pouckovab, Olivia Policianovaa, Jiri Brusa, Sebastian Eignerb, Ludek Sevcb, Petr Stepaneka, Martin Hrubya a Institute of Macromolecular Chemistry AS CR, v.v.i., Heyrovsky Sq. 2, 162 06, Prague, 6, Czech Republic b Institute of Biophysics and Informatics, First Faculty of Medicine, Charles University in Prague, Salmovska1, 120 00 Prague2, Czech Republic ⁎Corresponding author. E-mail address: [email protected] (M. Vetrik)
Fig. 1. Illustration of light-triggered drug delivery system.
Wilson’s disease is a genetic disorder causing excessive accumulation of copper in the body leading to toxic damage especially in the liver and in the nervous system. The current treatment is based on low-molecular weight copper chelators and zinc salts that have some burdensome side effects that arise as a consequence of absorption into the blood and organs after ingestion [1]. We design new biomaterials based on cellulose and crosslinked chitosan with covalently bounded copper chelator as potential drugs for the treatment of Wilson’s disease (Fig. 1). We proceeded from the fact that copper is absorbed into the body by the gastrointestinal tract. Therefore, new designed biopolymers should not be degradable in human digestive tract and should serve as copper scavengers. Our new proposed therapy utilizes specific copper chelating agent (8-hydroxyquinoline) that is covalently bound to carriers, cellulose or chitosan. New biocompatible carriers provide scavenging copper from gastrointestinal tract without organ deposition. Described compounds are eliminated through the feces after oral administration. We tested this idea in Wistar rats, which received radioactive 64Cu, with cellulose or chitosan with covalently bound 8-hydroxyquinoline. We