- Email: [email protected]
Asymmetrical polymer vesicles for significantly improving MRI sensitivity and cancer-targeted drug delivery
ChinaNanomedicine Abstracts / Nanomedicine: Nanotechnology, Biology, and Medicine 12 (2016) 449–575
extraction (PFSPE) and their applications for determination of neuro-active small molecules.
Scheme 1. Flowchart of PFSPE for neuro-active small molecules.
http://dx.doi.org/10.1016/j.nano.2015.12.105
Asymmetrical polymer vesicles for significantly improving MRI sensitivity and cancer-targeted drug delivery Qiuming Liu, Jianzhong Du⁎, Shanghai 10th People's Hospital, Tongji University School of Medicine, Shanghai, China, School of Material Science and Engineering, Tongji University, Shanghai, China ⁎Corresponding author. E-mail address: [email protected] (J. Du) Polymer vesicles have wide applications in drug delivery, antibacterial and water remediation, etc. Theranostic polymer vesicles that can simultaneously deliver diagnostic and therapeutic agents, have been developed for more accurate diagnosis and more efficient cancer chemotherapy. Magnetic resonance imaging (MRI) is one of the most powerful and non-invasive clinical imaging modalities with high spatial resolution. Traditional T1 MRI contrast agents such as diethylene triamine pentacetatic acid (DTPA) chelated gadolinium [Gd(III)] have poor sensitivity, leading to a risk of accumulated toxicity in vivo. To significantly improve the sensitivity of a T1 MRI contrast agent and to enhance the efficacy of cancer chemotherapy, herein for the first time we report a noncytotoxic asymmetrical cancer targeting polymer vesicle based on R-poly(l-glutamic acid)-block-poly(caprolactone) [R is folic acid (FA) or DTPA]. Such asymmetrical vesicles have a cancer-targeting outer corona and a Gd(III)-chelating and drug-loading-enhancing inner corona, exhibiting an extremely high T1 relaxivity (42.39 mM− 1 s− 1, 8-fold better than DTPA-Gd) and anticancer drug loading efficiency (52.6% for doxorubicin hydrochloride, DOX · HCl). Moreover, the DOX-loaded vesicles exhibited excellent antitumor activity (two-fold better than free DOX). This “chelatingjust-inside” strategy for synthesizing asymmetrical polymer vesicles provided promising potential theranostic applications in magnetic resonance imaging and cancer-targeted drug delivery.
http://dx.doi.org/10.1016/j.nano.2015.12.106
ATP-responsive codelivery of doxorubicin and nucleic acids for the synergistic cancer therapy Jianxu Zhanga, Haobo Hana, Di Wua, Xuesi Chenb, Quanshun Lia,b,⁎, aKey Laboratory for Molecular Enzymology and Engineering of Ministry of Education, School of Life Sciences, Jilin University, Changchun, China, bKey Laboratory of Polymer Ecomaterials, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun, China ⁎Corresponding author. E-mail address: [email protected] (Q. Li)
483
Stimuli-triggered drug delivery systems have attracted great attention as they could realize the physiological specificity and on-demand therapeutic efficacy of anticancer drugs or genes. Recently, ATP has been found with a low concentration in the extracellular environment (b0.4 mM) and a relatively high level within the intracellular cytosol (10 mM). Thus, the different ATP levels between the extracellular and intracellular environments could be used as a basis for designing the ATP-responsive drug delivery systems, especially for realizing the co-delivery of chemotherapeutics and nucleic acids. In this study, a novel co-delivery system DOX-aptamer/PEI25K/nucleic acids nanocomplex around 350 nm was designed and systematically evaluated, as shown in Scheme 1. We first designed a DNA scaffold by hybridizing an ATP aptamer and its cDNA, which has a 27-base pair with GC-rich motif for anthracycline-contained DOX loading. The in vitro release profile demonstrated an efficient DOX release (more than 90%) from DOXaptamer at an ATP concentration of 4 mM, a level comparable to intracellular ATP level. Then we mixed DOX-aptamer with different nucleic acids, the plasmid harboring p53 gene or Bcl-2 siRNA, and further PEI25K was deposited into the mixture at a ratio of 2:1 (carrier to nucleic acids, w/w) to obtain the nanocomplexes. In vitro analysis showed that these two nanocomplexes (DOX-aptamer/PEI/p53 plasmid and DOX-aptamer/PEI/Bcl-2 siRNA) exhibited synergistic effects on the proliferation inhibition of PC-3 cells. The combination treatment was found to lead to almost complete suppression of tumor cell growth, increased p53 expression or Bcl-2 silencing, and enhanced tumor apoptosis and cell cycle arrest. In addition, the expression level of proteins associated with cell apoptosis and cell cycle regulation was measured. In summary, the developed DOX-aptamer/PEI/nucleic acid nanocomplexes could be used as a potential safe and efficient delivery system for cancer therapy, and the ATP-responsive drug/gene co-delivery system provides a new idea of utilizing the tumor metabolism for exploring more efficient responsive delivery systems.
Scheme 1. ATP-responsive co-delivery of doxorubicin and nucleic acids for the synergistic cancer therapy.
http://dx.doi.org/10.1016/j.nano.2015.12.107
Berberine-loaded solid lipid nanoparticles enhance hypoglycemic efficacy on streptozotocin-induced diabetic C57BL/6 mice Zhiping Wanga, Yan Lib, Qun Zhouc, Yifei Wangd, Tongsheng Chene, aSchool of Pharmacy, Guangdong Pharmaceutical University, Guangzhou, China, b School of Chinese Materia Medica, Guangzhou University of Chinese Medicine, Guangzhou, China, cHubei Key Laboratory of Natural Medicinal Chemistry and Resource Evaluation, Tongji School of Pharmacy, Huazhong University of Science and Technology, Wuhan, China, dInstitute of Biological Medicine, Jinan University, Guangzhou, China, eMOE Key Laboratory of Laser Life Science & Institute of Laser Life Science, South China Normal University, Guangzhou, China E-mail address: [email protected] (Z. Wang) Berberine (Ber), an isoquinoline derivative alkaloid and active ingredient of Coptis, has been demonstrated to possess anti-diabetic activities. However its
extraction (PFSPE) and their applications for determination of neuro-active small molecules.
Scheme 1. Flowchart of PFSPE for neuro-active small molecules.
http://dx.doi.org/10.1016/j.nano.2015.12.105
Asymmetrical polymer vesicles for significantly improving MRI sensitivity and cancer-targeted drug delivery Qiuming Liu, Jianzhong Du⁎, Shanghai 10th People's Hospital, Tongji University School of Medicine, Shanghai, China, School of Material Science and Engineering, Tongji University, Shanghai, China ⁎Corresponding author. E-mail address: [email protected] (J. Du) Polymer vesicles have wide applications in drug delivery, antibacterial and water remediation, etc. Theranostic polymer vesicles that can simultaneously deliver diagnostic and therapeutic agents, have been developed for more accurate diagnosis and more efficient cancer chemotherapy. Magnetic resonance imaging (MRI) is one of the most powerful and non-invasive clinical imaging modalities with high spatial resolution. Traditional T1 MRI contrast agents such as diethylene triamine pentacetatic acid (DTPA) chelated gadolinium [Gd(III)] have poor sensitivity, leading to a risk of accumulated toxicity in vivo. To significantly improve the sensitivity of a T1 MRI contrast agent and to enhance the efficacy of cancer chemotherapy, herein for the first time we report a noncytotoxic asymmetrical cancer targeting polymer vesicle based on R-poly(l-glutamic acid)-block-poly(caprolactone) [R is folic acid (FA) or DTPA]. Such asymmetrical vesicles have a cancer-targeting outer corona and a Gd(III)-chelating and drug-loading-enhancing inner corona, exhibiting an extremely high T1 relaxivity (42.39 mM− 1 s− 1, 8-fold better than DTPA-Gd) and anticancer drug loading efficiency (52.6% for doxorubicin hydrochloride, DOX · HCl). Moreover, the DOX-loaded vesicles exhibited excellent antitumor activity (two-fold better than free DOX). This “chelatingjust-inside” strategy for synthesizing asymmetrical polymer vesicles provided promising potential theranostic applications in magnetic resonance imaging and cancer-targeted drug delivery.
http://dx.doi.org/10.1016/j.nano.2015.12.106
ATP-responsive codelivery of doxorubicin and nucleic acids for the synergistic cancer therapy Jianxu Zhanga, Haobo Hana, Di Wua, Xuesi Chenb, Quanshun Lia,b,⁎, aKey Laboratory for Molecular Enzymology and Engineering of Ministry of Education, School of Life Sciences, Jilin University, Changchun, China, bKey Laboratory of Polymer Ecomaterials, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun, China ⁎Corresponding author. E-mail address: [email protected] (Q. Li)
483
Stimuli-triggered drug delivery systems have attracted great attention as they could realize the physiological specificity and on-demand therapeutic efficacy of anticancer drugs or genes. Recently, ATP has been found with a low concentration in the extracellular environment (b0.4 mM) and a relatively high level within the intracellular cytosol (10 mM). Thus, the different ATP levels between the extracellular and intracellular environments could be used as a basis for designing the ATP-responsive drug delivery systems, especially for realizing the co-delivery of chemotherapeutics and nucleic acids. In this study, a novel co-delivery system DOX-aptamer/PEI25K/nucleic acids nanocomplex around 350 nm was designed and systematically evaluated, as shown in Scheme 1. We first designed a DNA scaffold by hybridizing an ATP aptamer and its cDNA, which has a 27-base pair with GC-rich motif for anthracycline-contained DOX loading. The in vitro release profile demonstrated an efficient DOX release (more than 90%) from DOXaptamer at an ATP concentration of 4 mM, a level comparable to intracellular ATP level. Then we mixed DOX-aptamer with different nucleic acids, the plasmid harboring p53 gene or Bcl-2 siRNA, and further PEI25K was deposited into the mixture at a ratio of 2:1 (carrier to nucleic acids, w/w) to obtain the nanocomplexes. In vitro analysis showed that these two nanocomplexes (DOX-aptamer/PEI/p53 plasmid and DOX-aptamer/PEI/Bcl-2 siRNA) exhibited synergistic effects on the proliferation inhibition of PC-3 cells. The combination treatment was found to lead to almost complete suppression of tumor cell growth, increased p53 expression or Bcl-2 silencing, and enhanced tumor apoptosis and cell cycle arrest. In addition, the expression level of proteins associated with cell apoptosis and cell cycle regulation was measured. In summary, the developed DOX-aptamer/PEI/nucleic acid nanocomplexes could be used as a potential safe and efficient delivery system for cancer therapy, and the ATP-responsive drug/gene co-delivery system provides a new idea of utilizing the tumor metabolism for exploring more efficient responsive delivery systems.
Scheme 1. ATP-responsive co-delivery of doxorubicin and nucleic acids for the synergistic cancer therapy.
http://dx.doi.org/10.1016/j.nano.2015.12.107
Berberine-loaded solid lipid nanoparticles enhance hypoglycemic efficacy on streptozotocin-induced diabetic C57BL/6 mice Zhiping Wanga, Yan Lib, Qun Zhouc, Yifei Wangd, Tongsheng Chene, aSchool of Pharmacy, Guangdong Pharmaceutical University, Guangzhou, China, b School of Chinese Materia Medica, Guangzhou University of Chinese Medicine, Guangzhou, China, cHubei Key Laboratory of Natural Medicinal Chemistry and Resource Evaluation, Tongji School of Pharmacy, Huazhong University of Science and Technology, Wuhan, China, dInstitute of Biological Medicine, Jinan University, Guangzhou, China, eMOE Key Laboratory of Laser Life Science & Institute of Laser Life Science, South China Normal University, Guangzhou, China E-mail address: [email protected] (Z. Wang) Berberine (Ber), an isoquinoline derivative alkaloid and active ingredient of Coptis, has been demonstrated to possess anti-diabetic activities. However its