- Email: [email protected]
A novel biomacromolecule controlled-release system based on mesoporous silica nanoparticles with large pore size and small particle size
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Abstracts / Journal of Controlled Release 213 (2015) e8–e152
Keywords: Combination chemotherapy, Doxorubicin, Malignancy therapy, Micelle, Thermogel
Acknowledgments This work was financially supported by the National Natural Science Foundation of China (51303174, 51321062, 51233004, 51390484, 51273196 and 51203153).
References [1] S.Y. Zafar, J.L. Malin, S.C. Grambow, D.H. Abbott, J.T. Kolimaga, L.L. Zullig, J.C. Weeks, J.Z. Ayanian, K.L. Kahn, P.A. Ganz, P.J. Catalano, D.W. West, D. Provenzale, R. for the Cancer Care Outcomes, C. Surveillance, Chemotherapy use and patient treatment preferences in advanced colorectal cancer, Cancer 119 (2013) 854–862. [2] J.X. Ding, W.G. Xu, Y. Zhang, D.K. Sun, C.S. Xiao, D.H. Liu, X.J. Zhu, X.S. Chen, Self-reinforced endocytoses of smart polypeptide nanogels for “on-demand” drug delivery, J. Control. Release 172 (2013) 444–455. [3] J. Bai, Y. Liu, X. Jiang, Multifunctional PEG-GO/CuS nanocomposites for near-infrared chemo-photothermal therapy, Biomaterials 35 (2014) 5805–5813.
doi:10.1016/j.jconrel.2015.05.190
Anisamide-functionalized intelligent polymersomes mediate targeted delivery of methotrexate into lung cancer cells
Fig. 1. CLSM images of H460 cells treated with MTX-50Anis-PS for 3 h (A) and 6 h (B). For each panel, the images from left to right show FITC-MTX fluorescence in cells (green), cell nuclei stained by DAPI (blue), lysosomes stained with LysoTracker Red (red), and overlays of the three images. The scale bars correspond to 15 μm in all the images.
Keywords: Polymersomes, Tumor-targeting, Reversibly crosslinking, Reduction-sensitive Acknowledgments This work is supported by the National Natural Science Foundation of China (51173126, 51273139, 81261120557), Ph.D. Programs Foundation of Ministry of Education of the People's Republic of China (20133201110005), and the Major Program of the National Natural Science Foundation of Jiangsu Province (14KJA150008). Reference [1] F.H. Meng, Z.Y. Zhong, J. Feijen, Stimuli-responsive polymersomes for programmed drug delivery, Biomacromolecules 10 (2009) 197–209. doi:10.1016/j.jconrel.2015.05.191
Weijing Yang, Fenghua Meng*, Zhiyuan Zhong* Biomedical Polymers Laboratory, and Jiangsu Key Laboratory of Advanced Functional Polymer Design and Application, College of Chemistry, Chemical Engineering and Materials Science, Soochow University, Suzhou 215123, China ⁎Corresponding authors. E-mail addresses: [email protected] (W. Yang), [email protected] (F. Meng), [email protected] (Z. Zhong). Polymersomes are one of the most ideal systems for intracellular delivery of water-soluble apoptotic drugs including low molecular weight chemotherapeutics and protein drugs [1]. Here, we report on anisamide-functionalized reduction-sensitive reversibly crosslinked polymersomes (Anis-PS) for targeted delivery of methotrexate (MTX) to H460 lung cancer cells. Anis-PS was prepared from anisamidepoly(ethylene glycol)-b-poly(N-(2-hydroxypropyl)methacrylamide-glipoic acid)-b-poly-2-(dimethyl amino)ethyl methacrylate (Anis-PEGP(HPMA-LA)-PDMA) and non-targeting PEG-P(HPMA-LA)-PDMA copolymers. MTX-loaded Anis-PS (MTX-Anis-PS) depending on ratios of two copolymers had drug loading contents of 10–19 wt.% and average sizes of 150–180 nm (PDI 0.04–0.17). The release of MTX showed a clear reduction-dependent behavior. MTT assays showed that MTX-Anis-PS with 50% Anis (MTX-50Anis-PS) exhibited 2.8-fold lower halfmaximal inhibitory concentration (IC50) in sigma receptor overexpressing H460 cells than non-targeting MTX-PS. The inhibition experiments with haloperidol confirmed that MTX-Anis-PS is internalized by H460 cells via a receptor mediated endocytosis mechanism. It is interesting to note that MTX-50Anis-PS delivered and released FITCMTX into the cytoplasms and nuclei of H460 cells in 6 h (Fig. 1). The efficient endosomal escape and intracellular drug release are likely due to a combination of the proton-sponge effect of PDMA and reductiontriggered de-crosslinking of polymersomes.
A novel biomacromolecule controlled-release system based on mesoporous silica nanoparticles with large pore size and small particle size Mingyang Hei, Weiping Zhu*, Yujie Li, Yufang Xu, Xuhong Qian State Key Laboratory of Bioreactor Engineering, Shanghai Key Lab of Chemical Biology, School of Pharmacy, East China University of Science and Technology, Shanghai 200237, China ⁎Corresponding author. E-mail address: [email protected] (W. Zhu). In recent years, versatile functionalized mesoporous silica nanoparticle (MSN)-based stimuli-responsive controlled-release systems have been investigated [1,2]. However, mutual restrictions between pore size and particle size of MSNs limit their further applications, especially in the development of controlled release systems of biomacromolecules, such as insulin, antigen, and siRNA [2]. Herein, we constructed a novel smart saccharide-responsive delivery system, FZ@MSN–PBE–Insulin (MPIFZ), based on MSN with large pores (8–10 nm) and small particle sizes (170– 200 nm), using phenyl borate esters (PBE) with different structures as saccharide-sensitive linker and functional zinc oxide nanoparticle (FZ) as the capping agent (Fig. 1). The release profiles demonstrated that MPIFZ had a high loading capacity of insulin hexamer (diameter about 5.18 nm) and no “zero premature release” was observed. By changing the structure of PBE, the controlled release property of MPIFZ could be modulated. In the presence of the corresponding substrate, i.e. fructose or glucose, MPIFZ could release insulin within 20 min according to different substrate concentrations. These results demonstrated an innovative approach to the development of a novel bio-macromolecule delivery system.
Abstracts / Journal of Controlled Release 213 (2015) e8–e152
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Chol) host–guest interactions, composed of a hydrophobic component (PLA) as outer and inner membranes, and hydrophilic component (CD) as central layer (Fig. 1a). The Z-average diameter was ca. 150–350 nm with a thickness of ca. 22–30 nm (Fig. 1b), and could be well tuned by changing the branching and the molecular weight of the backbone to meet different kinds of application requirements. At low dye concentration (b0.5 g/L), all the reverse vesicles were able to quantitatively extract Congo red (CR) from the aqueous layer (Fig. 1c). The amount of CR extracted from the aqueous phase increased with the CR concentration. Interestingly, reverse vesicles with a 3:1 molar ratio of the CD/Chol units yielded significantly larger loading efficiencies on account of the free CD molecules, which is favorable for extracting because of the host–guest interactions between CD and CR, demonstrating a great potential as drug carriers or nanoreactors.
Fig. 1. Schematic diagram of MPIFZ controlled-release system.
Keywords: Mesoporous silica nanoparticles, Phenyl borate esters, Biomacromolecules, Controlled release Acknowledgments This work is supported by the National Natural Science Foundation of China (21236002) and 973 Program (2013CB733700). References [1] M.W. Ambrogio, C.R. Thomas, Y.L. Zhao, J.I. Zink, J.F. Stoddart, Mechanized silica nanoparticles: a new frontier in theranostic nanomedicine, Acc. Chem. Res. 44 (2011) 903–913. [2] B.G. Trewyn, S. Giri, I.I. Slowing, V.S.Y. Lin, Mesoporous silica nanoparticle based controlled release, drug delivery, and biosensor systems, Chem. Commun. 31 (2007) 3236–3245. doi:10.1016/j.jconrel.2015.05.192
Construction of reverse vesicles based on cyclodextrin–cholesterol inclusion complexation Wen-Xing Gua, Ying-Wei Yangb, Ji-Jie Wena, Hui Gaoa,* a School of Chemistry and Chemical Engineering, Tianjin University of Technology, Tianjin 300384, China b College of Chemistry, Jilin University, Changchun 130012, China ⁎Corresponding author. E-mail address: [email protected] (W.-X. Gu). The synthesis and modification of poly(glycidyl methacrylate) (PGMA) have arose the interests of many researchers, and diverse assemblies, including micelles, reverse micelles, capsules, and nanoparticles have been prepared [1]. As the counterparts of normal vesicles, we firmly believe that reverse vesicles hold a great potential in bio-related fields, especially as drug carriers. However, compared with the extensive knowledge of normal vesicles, research on reverse vesicles was scarce. Tracing back to the pioneers, Kunieda et al. reported on reverse vesicles formed in a nonionic surfactant system for the first time, only several novel reverse vesicular systems were discovered by successors [2]. Owing to the presence of innovative techniques and concepts (such as supramolecular chemistry, self-assembly), research on reverse vesicles is deemed to be one of the most important and rapidly evolving areas. In this study, novel reverse vesicles, consisting of a hydrophobic core surrounded by a reverse bilayer, were constructed from pseudo-graft amphiphilic PGMA-based copolymers. We firstly developed a facile construction of pseudo-graft amphiphilic copolymer reverse vesicles via β-cyclodextrin–cholesterol (CD–
Fig. 1. Schematic representation (a), TEM image (b), and encapsulation photograph (c) of reverse vesicles.
Keywords: Reverse vesicles, Poly(glycerol methacrylate), β-Cyclodextrin, Cholesterol Acknowledgments This work was supported by the National Natural Science Foundation of China (21374079), and Program for New Century Excellent Talents in University (NCET-11-1063). References [1] Q.L. Li, W.X. Gu, H. Gao, Y.W. Yang, Self-assembly and applications of poly(glycidyl methacrylate)s and their derivatives, Chem. Commun. (2014)http://dx.doi.org/10.1039/C4CC03036B. [2] K.D. Zhang, T.Y. Zhou, X. Zhao, X.K. Jiang, Z.T. Li, Redoxresponsive reverse vesicles self-assembled by pseudo[2]rotaxanes for tunable dye release, Langmuir 28 (2012) 14839–14844. doi:10.1016/j.jconrel.2015.05.193
IgY-loaded calcium phosphate nanospheres: Preparation, sustained release and antibacterial activity Xi Chena, Feng Chenb, Xi-Ping Fenga,*, Ying-Jie Zhub,* a Department of Preventive Dentistry, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200011, China b State Key Laboratory of High Performance Ceramics and Superfine Microstructure, Shanghai Institute of Ceramics, Chinese Academy of Sciences, Shanghai 200050, China ⁎Corresponding authors. E-mail addresses: [email protected] (X.-P. Feng), [email protected] (Y.-J. Zhu). The exploration of safe and effective fluoride-free anti-caries materials has become an important field in the study of caries prevention. Ideal anti-caries material should possess such functions as anti-bacterial, re-mineralization and biocompatibility [1].
Abstracts / Journal of Controlled Release 213 (2015) e8–e152
Keywords: Combination chemotherapy, Doxorubicin, Malignancy therapy, Micelle, Thermogel
Acknowledgments This work was financially supported by the National Natural Science Foundation of China (51303174, 51321062, 51233004, 51390484, 51273196 and 51203153).
References [1] S.Y. Zafar, J.L. Malin, S.C. Grambow, D.H. Abbott, J.T. Kolimaga, L.L. Zullig, J.C. Weeks, J.Z. Ayanian, K.L. Kahn, P.A. Ganz, P.J. Catalano, D.W. West, D. Provenzale, R. for the Cancer Care Outcomes, C. Surveillance, Chemotherapy use and patient treatment preferences in advanced colorectal cancer, Cancer 119 (2013) 854–862. [2] J.X. Ding, W.G. Xu, Y. Zhang, D.K. Sun, C.S. Xiao, D.H. Liu, X.J. Zhu, X.S. Chen, Self-reinforced endocytoses of smart polypeptide nanogels for “on-demand” drug delivery, J. Control. Release 172 (2013) 444–455. [3] J. Bai, Y. Liu, X. Jiang, Multifunctional PEG-GO/CuS nanocomposites for near-infrared chemo-photothermal therapy, Biomaterials 35 (2014) 5805–5813.
doi:10.1016/j.jconrel.2015.05.190
Anisamide-functionalized intelligent polymersomes mediate targeted delivery of methotrexate into lung cancer cells
Fig. 1. CLSM images of H460 cells treated with MTX-50Anis-PS for 3 h (A) and 6 h (B). For each panel, the images from left to right show FITC-MTX fluorescence in cells (green), cell nuclei stained by DAPI (blue), lysosomes stained with LysoTracker Red (red), and overlays of the three images. The scale bars correspond to 15 μm in all the images.
Keywords: Polymersomes, Tumor-targeting, Reversibly crosslinking, Reduction-sensitive Acknowledgments This work is supported by the National Natural Science Foundation of China (51173126, 51273139, 81261120557), Ph.D. Programs Foundation of Ministry of Education of the People's Republic of China (20133201110005), and the Major Program of the National Natural Science Foundation of Jiangsu Province (14KJA150008). Reference [1] F.H. Meng, Z.Y. Zhong, J. Feijen, Stimuli-responsive polymersomes for programmed drug delivery, Biomacromolecules 10 (2009) 197–209. doi:10.1016/j.jconrel.2015.05.191
Weijing Yang, Fenghua Meng*, Zhiyuan Zhong* Biomedical Polymers Laboratory, and Jiangsu Key Laboratory of Advanced Functional Polymer Design and Application, College of Chemistry, Chemical Engineering and Materials Science, Soochow University, Suzhou 215123, China ⁎Corresponding authors. E-mail addresses: [email protected] (W. Yang), [email protected] (F. Meng), [email protected] (Z. Zhong). Polymersomes are one of the most ideal systems for intracellular delivery of water-soluble apoptotic drugs including low molecular weight chemotherapeutics and protein drugs [1]. Here, we report on anisamide-functionalized reduction-sensitive reversibly crosslinked polymersomes (Anis-PS) for targeted delivery of methotrexate (MTX) to H460 lung cancer cells. Anis-PS was prepared from anisamidepoly(ethylene glycol)-b-poly(N-(2-hydroxypropyl)methacrylamide-glipoic acid)-b-poly-2-(dimethyl amino)ethyl methacrylate (Anis-PEGP(HPMA-LA)-PDMA) and non-targeting PEG-P(HPMA-LA)-PDMA copolymers. MTX-loaded Anis-PS (MTX-Anis-PS) depending on ratios of two copolymers had drug loading contents of 10–19 wt.% and average sizes of 150–180 nm (PDI 0.04–0.17). The release of MTX showed a clear reduction-dependent behavior. MTT assays showed that MTX-Anis-PS with 50% Anis (MTX-50Anis-PS) exhibited 2.8-fold lower halfmaximal inhibitory concentration (IC50) in sigma receptor overexpressing H460 cells than non-targeting MTX-PS. The inhibition experiments with haloperidol confirmed that MTX-Anis-PS is internalized by H460 cells via a receptor mediated endocytosis mechanism. It is interesting to note that MTX-50Anis-PS delivered and released FITCMTX into the cytoplasms and nuclei of H460 cells in 6 h (Fig. 1). The efficient endosomal escape and intracellular drug release are likely due to a combination of the proton-sponge effect of PDMA and reductiontriggered de-crosslinking of polymersomes.
A novel biomacromolecule controlled-release system based on mesoporous silica nanoparticles with large pore size and small particle size Mingyang Hei, Weiping Zhu*, Yujie Li, Yufang Xu, Xuhong Qian State Key Laboratory of Bioreactor Engineering, Shanghai Key Lab of Chemical Biology, School of Pharmacy, East China University of Science and Technology, Shanghai 200237, China ⁎Corresponding author. E-mail address: [email protected] (W. Zhu). In recent years, versatile functionalized mesoporous silica nanoparticle (MSN)-based stimuli-responsive controlled-release systems have been investigated [1,2]. However, mutual restrictions between pore size and particle size of MSNs limit their further applications, especially in the development of controlled release systems of biomacromolecules, such as insulin, antigen, and siRNA [2]. Herein, we constructed a novel smart saccharide-responsive delivery system, FZ@MSN–PBE–Insulin (MPIFZ), based on MSN with large pores (8–10 nm) and small particle sizes (170– 200 nm), using phenyl borate esters (PBE) with different structures as saccharide-sensitive linker and functional zinc oxide nanoparticle (FZ) as the capping agent (Fig. 1). The release profiles demonstrated that MPIFZ had a high loading capacity of insulin hexamer (diameter about 5.18 nm) and no “zero premature release” was observed. By changing the structure of PBE, the controlled release property of MPIFZ could be modulated. In the presence of the corresponding substrate, i.e. fructose or glucose, MPIFZ could release insulin within 20 min according to different substrate concentrations. These results demonstrated an innovative approach to the development of a novel bio-macromolecule delivery system.
Abstracts / Journal of Controlled Release 213 (2015) e8–e152
e115
Chol) host–guest interactions, composed of a hydrophobic component (PLA) as outer and inner membranes, and hydrophilic component (CD) as central layer (Fig. 1a). The Z-average diameter was ca. 150–350 nm with a thickness of ca. 22–30 nm (Fig. 1b), and could be well tuned by changing the branching and the molecular weight of the backbone to meet different kinds of application requirements. At low dye concentration (b0.5 g/L), all the reverse vesicles were able to quantitatively extract Congo red (CR) from the aqueous layer (Fig. 1c). The amount of CR extracted from the aqueous phase increased with the CR concentration. Interestingly, reverse vesicles with a 3:1 molar ratio of the CD/Chol units yielded significantly larger loading efficiencies on account of the free CD molecules, which is favorable for extracting because of the host–guest interactions between CD and CR, demonstrating a great potential as drug carriers or nanoreactors.
Fig. 1. Schematic diagram of MPIFZ controlled-release system.
Keywords: Mesoporous silica nanoparticles, Phenyl borate esters, Biomacromolecules, Controlled release Acknowledgments This work is supported by the National Natural Science Foundation of China (21236002) and 973 Program (2013CB733700). References [1] M.W. Ambrogio, C.R. Thomas, Y.L. Zhao, J.I. Zink, J.F. Stoddart, Mechanized silica nanoparticles: a new frontier in theranostic nanomedicine, Acc. Chem. Res. 44 (2011) 903–913. [2] B.G. Trewyn, S. Giri, I.I. Slowing, V.S.Y. Lin, Mesoporous silica nanoparticle based controlled release, drug delivery, and biosensor systems, Chem. Commun. 31 (2007) 3236–3245. doi:10.1016/j.jconrel.2015.05.192
Construction of reverse vesicles based on cyclodextrin–cholesterol inclusion complexation Wen-Xing Gua, Ying-Wei Yangb, Ji-Jie Wena, Hui Gaoa,* a School of Chemistry and Chemical Engineering, Tianjin University of Technology, Tianjin 300384, China b College of Chemistry, Jilin University, Changchun 130012, China ⁎Corresponding author. E-mail address: [email protected] (W.-X. Gu). The synthesis and modification of poly(glycidyl methacrylate) (PGMA) have arose the interests of many researchers, and diverse assemblies, including micelles, reverse micelles, capsules, and nanoparticles have been prepared [1]. As the counterparts of normal vesicles, we firmly believe that reverse vesicles hold a great potential in bio-related fields, especially as drug carriers. However, compared with the extensive knowledge of normal vesicles, research on reverse vesicles was scarce. Tracing back to the pioneers, Kunieda et al. reported on reverse vesicles formed in a nonionic surfactant system for the first time, only several novel reverse vesicular systems were discovered by successors [2]. Owing to the presence of innovative techniques and concepts (such as supramolecular chemistry, self-assembly), research on reverse vesicles is deemed to be one of the most important and rapidly evolving areas. In this study, novel reverse vesicles, consisting of a hydrophobic core surrounded by a reverse bilayer, were constructed from pseudo-graft amphiphilic PGMA-based copolymers. We firstly developed a facile construction of pseudo-graft amphiphilic copolymer reverse vesicles via β-cyclodextrin–cholesterol (CD–
Fig. 1. Schematic representation (a), TEM image (b), and encapsulation photograph (c) of reverse vesicles.
Keywords: Reverse vesicles, Poly(glycerol methacrylate), β-Cyclodextrin, Cholesterol Acknowledgments This work was supported by the National Natural Science Foundation of China (21374079), and Program for New Century Excellent Talents in University (NCET-11-1063). References [1] Q.L. Li, W.X. Gu, H. Gao, Y.W. Yang, Self-assembly and applications of poly(glycidyl methacrylate)s and their derivatives, Chem. Commun. (2014)http://dx.doi.org/10.1039/C4CC03036B. [2] K.D. Zhang, T.Y. Zhou, X. Zhao, X.K. Jiang, Z.T. Li, Redoxresponsive reverse vesicles self-assembled by pseudo[2]rotaxanes for tunable dye release, Langmuir 28 (2012) 14839–14844. doi:10.1016/j.jconrel.2015.05.193
IgY-loaded calcium phosphate nanospheres: Preparation, sustained release and antibacterial activity Xi Chena, Feng Chenb, Xi-Ping Fenga,*, Ying-Jie Zhub,* a Department of Preventive Dentistry, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200011, China b State Key Laboratory of High Performance Ceramics and Superfine Microstructure, Shanghai Institute of Ceramics, Chinese Academy of Sciences, Shanghai 200050, China ⁎Corresponding authors. E-mail addresses: [email protected] (X.-P. Feng), [email protected] (Y.-J. Zhu). The exploration of safe and effective fluoride-free anti-caries materials has become an important field in the study of caries prevention. Ideal anti-caries material should possess such functions as anti-bacterial, re-mineralization and biocompatibility [1].