- Email: [email protected]
Photo-crosslinked hollow capsules as platform for biomedical applications
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Abstracts / Journal of Controlled Release 259 (2017) e5–e195
Moreover, obviously accelerated drug release from star and linear copolymer based RCLMs was observed at pH 5.0, leading to higher cumulative drug release percentages of 39% and 48% in 24 h, respectively. The results demonstrate that these hydrazone bond based RCLMs are prospective nano-architectures for controlled delivery of hydrophobic drugs. Keywords: drug delivery, reversible cross-linked micelles, dynamic chemistry bond, star topology Acknowledgements This work was financially supported by National Natural Science Foundation of China (No. 21176090).
Fig. 1. Schematic representation of post-conjugated hollow capsules for application in drug delivery and synthetic biology. Adapted and reproduced with permission from reference 4. Copyright 2016 American Chemical Society.
References [1] Y. Shi, C.F. van Nostrum, W.E. Hennink, Interfacially hydrazone cross-linked thermosensitive polymeric micelles for acid-triggered release of paclitaxel, ACS Biomater. Sci. Eng. 1 (2015) 393-404. [2] X. Zhao, P. Liu, Reduction-responsive core-shell-corona micelles based on triblock copolymers: novel synthetic strategy, characterization, and application as a tumor microenvironment- responsive drug delivery system, ACS Appl. Mater. Interfaces 7 (2015) 166-174.
doi:10.1016/j.jconrel.2017.03.079
Photo-crosslinked hollow capsules as platform for biomedical applications Dietmar Appelhansa,⁎, Hannes Gumza,b, Xiaoling Liua,b, Banu Iyisana,b, Brigitte Voita,b a Leibniz-Institut für Polymerforschung Dresden e. V., Hohe Straße 6, 01069 Dresden, Germany b Organische Chemie der Polymere, Technische Universität Dresden, D-01069 Dresden, Germany ⁎Corresponding author. E-mail address: [email protected] (D. Appelhans) Over the last years, huge efforts have been undertaken to develop feasible polymer-based systems for biomedical applications. Hollow capsules (e.g. polymersomes) among others have been proven to be promising candidates for such purposes. In this context (Fig. 1), our efforts were directed to establish pH-stable polymersomes over a broad pH range by the incorporation of two different photocrosslinkable moieties in the membrane. This allows us for undergoing reversible switching of polymersome´s membrane to trigger the uptake and release of small molecules under various pH values, but also to squeeze out larger macromolecules under shear forces [1, 2]. For developing even more complex polymeric vesicles usable in biomedical applications and synthetic biology, where post-noncovalent conjugation steps and/or de-conjugation/displacement steps are required, we report further progress on pH- and size-controlled diffusion processes. Results are presented and discussed in respect to pH-dependent (multi-)enzymatic conversion steps [3] and folic acid-enhanced uptake of doxorubicin-loaded polymersomes by folic acid-sensitive cells [2] as well post-conjugation processes inside and outside of polymersomes and mimicking cell membrane functions for the uptake and release of larger protein-like macromolecules (up to ∅ 11 nm) by/from pH and temperature dual-responsive hollow capsules [4]. These new developments will give the possibility to fabricate new types of multicompartmentalized capsules for biomedical applications.
Keywords: hollow capsules, membrane permeability, postencapsulation/-conjugation, synthetic biology References [1] J. Gaitzsch, I. Canton, D. Appelhans, G. Battaglia, B. Voit, Synthetic bio-nanoreactor: Mechanical and chemical control of polymersome membrane permeability, Angew. Chem. Int. Ed. 51 (2012) 4448-4451. [2] M. Yassin, D. Appelhans, R. Wiedemuth, P. Formanek, S. Boye, A. Lederer, A. Temme, B. Voit, Overcoming Concealment Effect of Targeting Groups in the PEG Corona: pH-Switchable Polymersomes Decorated with Folate-Antennae for Selective Targeting of Tumor Cells, Small 11 (2015) 1580-1591. [3] D. Gräfe, J. Gaitzsch, D. Appelhans, B. Voit, Crosslinked polymersomes as nanoreactors for controlled and stabilized single and cascade enzymatic reactions, Nanoscale 6 (2014) 10752-10761. [4] B. Iyisan, J. Kluge, P. Formanek, P.B. Voit, D. Appelhans, Multifunctional and dualresponsive Polymersomes as robust nanocontainer: Design, formation by sequential post-conjugations, and pH-controlled drug release, Chem. Mater. 28 (2016) 1513-1525.
doi:10.1016/j.jconrel.2017.03.080
Smart pH-sensitive polymeric nanocarriers for combination chemotherapy Dong Wan, Juheng Li, Weijiao Liu, Jie Pan⁎ School of Environmental and Chemical Engineering, Tianjin Polytechnic University, Tianjin 300387, China ⁎Corresponding author. E-mail addresses: [email protected] (D. Wan), [email protected] (J. Pan) pH-sensitive polymeric nanocarriers look like the most promising tool for cancer therapy [1, 2]. In this work, novel pH-sensitive amphiphilic copolymers were firstly synthesized to facricate smart pH-sensitive nanocarriers for combination chemotherapy (Fig. 1). pH-sensitive poly(L-histidine) was utilized in nanocarriers for the intelligent purposes including: (i) under normal physiological pH, the targeting molecule of folate would be hidden into the layer of PEG chains in nanocarriers, which disabled the active targeting function of nanocarriers; (ii) but in weak acid condition of tumor tissue, poly(L-histidine) was protonated and became water-soluble to expose folate on the surface of nanocarriers, switching on the active targeting function; (iii) nanocarriers entered easily into cells via folate receptor-mediated endocytosis; (iv) nanocarriers begined to dissociate in the endosome/lysosome, which led to quick intracellular drug release. Nanocarriers developed in this work have multiple functions including active targeting, long circulation, easy to enter the cell, and rapid intracellular drug release, which improve significantly the anticancer effects of the combination chemotherapy of cisplatin/docetaxel and reduce toxic side effects. The experiments
Abstracts / Journal of Controlled Release 259 (2017) e5–e195
Moreover, obviously accelerated drug release from star and linear copolymer based RCLMs was observed at pH 5.0, leading to higher cumulative drug release percentages of 39% and 48% in 24 h, respectively. The results demonstrate that these hydrazone bond based RCLMs are prospective nano-architectures for controlled delivery of hydrophobic drugs. Keywords: drug delivery, reversible cross-linked micelles, dynamic chemistry bond, star topology Acknowledgements This work was financially supported by National Natural Science Foundation of China (No. 21176090).
Fig. 1. Schematic representation of post-conjugated hollow capsules for application in drug delivery and synthetic biology. Adapted and reproduced with permission from reference 4. Copyright 2016 American Chemical Society.
References [1] Y. Shi, C.F. van Nostrum, W.E. Hennink, Interfacially hydrazone cross-linked thermosensitive polymeric micelles for acid-triggered release of paclitaxel, ACS Biomater. Sci. Eng. 1 (2015) 393-404. [2] X. Zhao, P. Liu, Reduction-responsive core-shell-corona micelles based on triblock copolymers: novel synthetic strategy, characterization, and application as a tumor microenvironment- responsive drug delivery system, ACS Appl. Mater. Interfaces 7 (2015) 166-174.
doi:10.1016/j.jconrel.2017.03.079
Photo-crosslinked hollow capsules as platform for biomedical applications Dietmar Appelhansa,⁎, Hannes Gumza,b, Xiaoling Liua,b, Banu Iyisana,b, Brigitte Voita,b a Leibniz-Institut für Polymerforschung Dresden e. V., Hohe Straße 6, 01069 Dresden, Germany b Organische Chemie der Polymere, Technische Universität Dresden, D-01069 Dresden, Germany ⁎Corresponding author. E-mail address: [email protected] (D. Appelhans) Over the last years, huge efforts have been undertaken to develop feasible polymer-based systems for biomedical applications. Hollow capsules (e.g. polymersomes) among others have been proven to be promising candidates for such purposes. In this context (Fig. 1), our efforts were directed to establish pH-stable polymersomes over a broad pH range by the incorporation of two different photocrosslinkable moieties in the membrane. This allows us for undergoing reversible switching of polymersome´s membrane to trigger the uptake and release of small molecules under various pH values, but also to squeeze out larger macromolecules under shear forces [1, 2]. For developing even more complex polymeric vesicles usable in biomedical applications and synthetic biology, where post-noncovalent conjugation steps and/or de-conjugation/displacement steps are required, we report further progress on pH- and size-controlled diffusion processes. Results are presented and discussed in respect to pH-dependent (multi-)enzymatic conversion steps [3] and folic acid-enhanced uptake of doxorubicin-loaded polymersomes by folic acid-sensitive cells [2] as well post-conjugation processes inside and outside of polymersomes and mimicking cell membrane functions for the uptake and release of larger protein-like macromolecules (up to ∅ 11 nm) by/from pH and temperature dual-responsive hollow capsules [4]. These new developments will give the possibility to fabricate new types of multicompartmentalized capsules for biomedical applications.
Keywords: hollow capsules, membrane permeability, postencapsulation/-conjugation, synthetic biology References [1] J. Gaitzsch, I. Canton, D. Appelhans, G. Battaglia, B. Voit, Synthetic bio-nanoreactor: Mechanical and chemical control of polymersome membrane permeability, Angew. Chem. Int. Ed. 51 (2012) 4448-4451. [2] M. Yassin, D. Appelhans, R. Wiedemuth, P. Formanek, S. Boye, A. Lederer, A. Temme, B. Voit, Overcoming Concealment Effect of Targeting Groups in the PEG Corona: pH-Switchable Polymersomes Decorated with Folate-Antennae for Selective Targeting of Tumor Cells, Small 11 (2015) 1580-1591. [3] D. Gräfe, J. Gaitzsch, D. Appelhans, B. Voit, Crosslinked polymersomes as nanoreactors for controlled and stabilized single and cascade enzymatic reactions, Nanoscale 6 (2014) 10752-10761. [4] B. Iyisan, J. Kluge, P. Formanek, P.B. Voit, D. Appelhans, Multifunctional and dualresponsive Polymersomes as robust nanocontainer: Design, formation by sequential post-conjugations, and pH-controlled drug release, Chem. Mater. 28 (2016) 1513-1525.
doi:10.1016/j.jconrel.2017.03.080
Smart pH-sensitive polymeric nanocarriers for combination chemotherapy Dong Wan, Juheng Li, Weijiao Liu, Jie Pan⁎ School of Environmental and Chemical Engineering, Tianjin Polytechnic University, Tianjin 300387, China ⁎Corresponding author. E-mail addresses: [email protected] (D. Wan), [email protected] (J. Pan) pH-sensitive polymeric nanocarriers look like the most promising tool for cancer therapy [1, 2]. In this work, novel pH-sensitive amphiphilic copolymers were firstly synthesized to facricate smart pH-sensitive nanocarriers for combination chemotherapy (Fig. 1). pH-sensitive poly(L-histidine) was utilized in nanocarriers for the intelligent purposes including: (i) under normal physiological pH, the targeting molecule of folate would be hidden into the layer of PEG chains in nanocarriers, which disabled the active targeting function of nanocarriers; (ii) but in weak acid condition of tumor tissue, poly(L-histidine) was protonated and became water-soluble to expose folate on the surface of nanocarriers, switching on the active targeting function; (iii) nanocarriers entered easily into cells via folate receptor-mediated endocytosis; (iv) nanocarriers begined to dissociate in the endosome/lysosome, which led to quick intracellular drug release. Nanocarriers developed in this work have multiple functions including active targeting, long circulation, easy to enter the cell, and rapid intracellular drug release, which improve significantly the anticancer effects of the combination chemotherapy of cisplatin/docetaxel and reduce toxic side effects. The experiments