- Email: [email protected]
PHBV scaffolds with shape memory capability
e144
Abstracts / Journal of Controlled Release 259 (2017) e5–e195
Charge-conversional polyprodrug amphiphiles for intracellular dual-responsive drug delivery Xianglong Hua,b,⁎, Shiyong Liub,⁎⁎ a MOE Key Laboratory of Laser Life Science, Institute of Laser Life Science, College of Biophotonics, South China Normal University, Guangzhou 510631, China b CAS Key Laboratory of Soft Matter Chemistry, Department of Polymer Science and Engineering, University of Science and Technology of China, Anhui 230026, China ⁎Correspondence to: X. Hu, MOE Key Laboratory of Laser Life Science, Institute of Laser Life Science, College of Biophotonics, South China Normal University, Guangzhou 510631, China. ⁎⁎Corresponding author. E-mail addresses: [email protected] (X. Hu), [email protected] (S. Liu) It is cruial to rationally design theranostic systems with high drug loading and tailorable functions in biomedicine. In our previous work, polyprodrug amphiphiles of camptothecin (CPT) with N50 wt.% was developed, in which the hierarchical self-assembly, and shape-related biofunctions were discussed [1]. After that, self-reporting theranostic nanoparticles were fabricated from long-circulating hyperbranched polyprodrug amphiphiles, in which synergistic turn-on of therapeutic potency and enhanced MR imaging was observed in response to tumor reductive milieu [2]. Herein, a novel type of polyprodrug amphiphiles with charge-conversional potency, P(DMA-co-TPAMA/FITC)-bPCPTMA, was developed to accelerate endo/lysosomal escape of nanocarries in tumor’s acidic microenvironment, which was accompanied with acidic and reductive milieu-triggered CPT parent drug release (Fig. 1). In vitro and in vivo explorations proved the therapeutic efficiency. These charge-conversional polyprodrug amphiphiles may serve as a promising platform for controlled delivery of antitumor drugs.
Natural Science Foundation for Distinguished Young Scholars of Guangdong Province (2016A030306013), the Guangdong Program for Support of Top-notch Young Professionals (2015TQ01R604), the Natural Science Foundation of Guangdong Province (2014A030310310), and the Scientific Research Projects of Guangzhou (201607010328). References [1] X.L. Hu, J. M. Hu, J. Tian, Z.S. Ge, G.Y. Zhang, K.F. Luo, S.Y. Liu, Polyprodrug amphiphiles: hierarchical assemblies for shape-regulated cellular internalization, trafficking and drug delivery, J. Am. Chem. Soc. 135 (2013) 17617–17629. [2] X.L. Hu, G.H. Liu, Y. Li, X.R. Wang, S.Y. Liu, Cell-penetrating hyperbranched polyprodrug amphiphiles for synergistic reductive milieu-triggered drug release and enhanced magnetic resonance signals, J. Am. Chem. Soc. 137 (2015) 362− 368.
doi:10.1016/j.jconrel.2017.03.291
Fabrication of fibrous PLLA/PHBV scaffolds with shape memory capability Xianliu Wang, Hongyu Yan, Ying Zhou, Xiangxin Lou, Yanzhong Zhang⁎ College of Chemistry, Chemical Engineering & Biotechnology, Donghua University, Shanghai 201620, China ⁎Corresponding author. E-mail addresses: [email protected] (X. Wang), [email protected] (Y. Zhang) Biodegradable polymer poly(L-lactide) (PLLA) with shape memory capability has been widely used for engineering different tissues [1]. However, several noted issues such as brittleness, high glass transition temperature Tg necessitate modification of the PLLA to improve its application efficacy in physiological conditions. This study proposed to modify PLLA by blending it with a biodegradable poly(3-hydroxybutyrate-co-3-hydroxyv alerate) (PHBV) for fabricating fibrous PLLA/PHBV scaffold via electrospinning. Different polymer solutions at the concentration of 10 wt% are prepared by dissolving PLLA/PHBV blends at varying ratios in a solvent mixture of chloroform/N,Ndimethylformamide (9:1 in volume). Thereafter, these polymer solutions are electrospun into PLLA/PHBV composite fibers and characterizd by different techniques. Finally, cytocompability of the fibrous PLLA/PHBV scaffolds are evaluated by culturing bone marrow stem cells (BMSCs) seeded at different densities onto them for cell proliferation assay. The results show that ultrafine fibers of PLLA/PHBV with an averged diameter of ca. 3 μm can be successfully fabricated
Fig. 1. Illustration of charge-conversional polyprodrug amphiphiles, P(DMA-co-TPAMA/ FITC)-b-PCPTMA, for intracellular dual-responsive drug delivery.
Keywords: charge-conversional, polyprodrug amphiphiles, dual-responsive, drug delivery Acknowledgements This work was supported by the National Natural Scientific Foundation of China (NNSFC) Project (51403042 and 51033005), the
Fig. 1. (a) Tg decreases with increasing the loading ratio of PHBV in the PLLA/PHBV composite fibers. (b) Demonstrattion of shape memory effect of the electrospun PLLA/ PHBV (7:3) fiber mat. (c) Proliferation data of BMSCs cultured on the fibrous PLLA/ PHBV scaffolds.
Abstracts / Journal of Controlled Release 259 (2017) e5–e195
through electrospinning. Incorporation of PHBV gives rise to significantly improved mechanical properties. Tg of the composite fibers decreases with increasing the PHBV loading ratio (Fig. 1a). Excellent shape memory properties with high shape fixing ratio (N98%) and shape recovery ratio (N96%) are observed and macroscopically demonstratged (Fig. 1b). Moreover, in comparison with the neat PLLA and PHBV fibrous scaffolds, the fibrous scaffolds of PLLA/PHBV are able to promote the BMSCs to grow better (Fig. 1c). These attractive results warrant further investigation in vitro and in vivo on the feasibility of applying the biomimicking fibrous PLLA/PHBV scaffold with shape memory effect for tissue engineering applications.
e145
IR-780, was capable of flowing at body temperature. We demonstrated that the NIR irradiation of the nanoparticles for short-time led to rapid DOX release from the hydrophobic flow cores, achieving NIR-activated super-sensitive drug release inside tumor cells, which in turn facilitated the overcoming of DOX resistance of cancer cells in vitro and in vivo.
Keywords: shape memory polymer, PLLA, PHBV, electrospinning, Tg, tissue engineering Acknowledgements The authors are grateful for the financial support from the Key Project of Science and Technology of Shanghai Municipality (14JC1490100), and the National Natural Science Foundation of China (51073032, 31570969). Reference [1] Y.S Wong, S.S Venkatraman, Recovery as a measure of oriented crystalline structure in poly(L-lactide) used as shape memory polymer, Acta Mater. 58 (2010) 49-58.
Fig. 1. Schematic illustration of the NIR-activated drug release from polymeric nanocarriers with flow core (A) or rigid core (B) at body temperature.
doi:10.1016/j.jconrel.2017.03.292 Keywords: photoactivation, NIR-responsive nanomaterials, photothermal therapy, super-sensitive drug release, cancer therapy Near infrared light-activated super-sensitive drug release using nanoparticles with a flow core
Acknowledgements The authors are grateful for the financial support from the National Natural Science Foundation of China (51473043).
Jun-Xia Wang, Xian-Zhu Yang⁎ School of Biological and Medical Engineering, Hefei University of Technology, Hefei 230009, China ⁎Corresponding author. E-mail address: [email protected] (X.-Z. Yang)
[1] V. Shanmugam, S. Selvakumar, C. S. Yeh, Near-infrared light-responsive nanomaterials in cancer therapeutics. Chem. Soc. Rev. 43 (2014) 6254-6287.
Photoactivated nanomaterials exhibit immense promise for biomedical applications because noninvasive light stimulus can be spatially and temporally controlled, resulting in great safety, specificity, and efficacy. Specifically, near infrared (NIR) light radiation has an effective penetration depth and is less attenuated in biological tissues. Thus, NIRsensitive nanomaterials are of particular interest in the delivery of active substances to cells or tissues [1]. The NIR irradiation generates heat by the photothermal effect of encapsulated photothermal agents, and the heat can promote drug release from the hydrophobic cores of polymeric nanoparticles. However, the most widely used biodegradable materials (i.e., poly(d,l-lactide) (PLA), poly(lactide-co-glycotide) (PLGA) and poly(ε-caprolactone) (PCL)) have high glass-transition temperatures or melting temperatures, and thus rigid chains inside nanoparticles. The rigid cores may hinder the chain motion relative to each other during photothermal conversion processes that limit the diffusion of drug molecules. Thus, these types of materials are not ideal core materials for use in NIR-induced drug release for cancer therapy. The entire molecular motions of polymers are known to be activated in viscous flow states. Therefore, if polymeric nanoparticles possess flowable cores, NIR-activated super-sensitive drug release can be expected. Herein, we report on the NIR-activated super-sensitive drug release from polyphosphoester-based nanoparticles. As shown in Fig. 1, an amphiphilic block copolymer of PEG and poly(2-hexoxy-2-oxo-1,3,2dioxaphospholane) (PHEP) was formulated into nanoparticles. The flexible chain PHEP, which formed the nanoparticular core to encapsulate a model chemodrug DOX and the NIR photothermal agent
Reference
doi:10.1016/j.jconrel.2017.03.293
Multifunctional nanoparticles combining host-guest interaction of CB[7] and AuNS for light-promoted endosome escape and high gene transfection Jianwei Du, Xiao Zhao, Youxiang Wang⁎ MOE Key Laboratory of Macromolecular Synthesis and Functionalization, Department of Polymer Science and Engineering, Zhejiang University, Hangzhou 310027, China ⁎Corresponding author. E-mail addresses: [email protected] (J. Du), [email protected] (Y. Wang) Cucurbit[7]uril (CB[7]), an important member of cucurbit[n]uril could form inclusion complexes with many guest molecules such as adamantane, viologen and naphthalene derivatives [1, 2]. Furthermore, it was very interesting to find that CB[7] could self-assemble on photo-thermal gold nanoparticles [3]. Thus, by combining hostguest interaction of CB[7] and gold nanosphere (AuNS), an easy strategy for ligand modification was designed (Fig. 1). In this work, we successfully synthesized methyl viologen modified polyethylenimine (Mv-S-S-PEI, MP) and naphthalene modified polyethyleneglycol (Np-CH=N-PEG, NP) via pH- and GSH-responsive bonds, respectively (1H NMR). Then, the ternary complex MP@CB[7]@NP was formed by host-guest interacting with CB[7]
Abstracts / Journal of Controlled Release 259 (2017) e5–e195
Charge-conversional polyprodrug amphiphiles for intracellular dual-responsive drug delivery Xianglong Hua,b,⁎, Shiyong Liub,⁎⁎ a MOE Key Laboratory of Laser Life Science, Institute of Laser Life Science, College of Biophotonics, South China Normal University, Guangzhou 510631, China b CAS Key Laboratory of Soft Matter Chemistry, Department of Polymer Science and Engineering, University of Science and Technology of China, Anhui 230026, China ⁎Correspondence to: X. Hu, MOE Key Laboratory of Laser Life Science, Institute of Laser Life Science, College of Biophotonics, South China Normal University, Guangzhou 510631, China. ⁎⁎Corresponding author. E-mail addresses: [email protected] (X. Hu), [email protected] (S. Liu) It is cruial to rationally design theranostic systems with high drug loading and tailorable functions in biomedicine. In our previous work, polyprodrug amphiphiles of camptothecin (CPT) with N50 wt.% was developed, in which the hierarchical self-assembly, and shape-related biofunctions were discussed [1]. After that, self-reporting theranostic nanoparticles were fabricated from long-circulating hyperbranched polyprodrug amphiphiles, in which synergistic turn-on of therapeutic potency and enhanced MR imaging was observed in response to tumor reductive milieu [2]. Herein, a novel type of polyprodrug amphiphiles with charge-conversional potency, P(DMA-co-TPAMA/FITC)-bPCPTMA, was developed to accelerate endo/lysosomal escape of nanocarries in tumor’s acidic microenvironment, which was accompanied with acidic and reductive milieu-triggered CPT parent drug release (Fig. 1). In vitro and in vivo explorations proved the therapeutic efficiency. These charge-conversional polyprodrug amphiphiles may serve as a promising platform for controlled delivery of antitumor drugs.
Natural Science Foundation for Distinguished Young Scholars of Guangdong Province (2016A030306013), the Guangdong Program for Support of Top-notch Young Professionals (2015TQ01R604), the Natural Science Foundation of Guangdong Province (2014A030310310), and the Scientific Research Projects of Guangzhou (201607010328). References [1] X.L. Hu, J. M. Hu, J. Tian, Z.S. Ge, G.Y. Zhang, K.F. Luo, S.Y. Liu, Polyprodrug amphiphiles: hierarchical assemblies for shape-regulated cellular internalization, trafficking and drug delivery, J. Am. Chem. Soc. 135 (2013) 17617–17629. [2] X.L. Hu, G.H. Liu, Y. Li, X.R. Wang, S.Y. Liu, Cell-penetrating hyperbranched polyprodrug amphiphiles for synergistic reductive milieu-triggered drug release and enhanced magnetic resonance signals, J. Am. Chem. Soc. 137 (2015) 362− 368.
doi:10.1016/j.jconrel.2017.03.291
Fabrication of fibrous PLLA/PHBV scaffolds with shape memory capability Xianliu Wang, Hongyu Yan, Ying Zhou, Xiangxin Lou, Yanzhong Zhang⁎ College of Chemistry, Chemical Engineering & Biotechnology, Donghua University, Shanghai 201620, China ⁎Corresponding author. E-mail addresses: [email protected] (X. Wang), [email protected] (Y. Zhang) Biodegradable polymer poly(L-lactide) (PLLA) with shape memory capability has been widely used for engineering different tissues [1]. However, several noted issues such as brittleness, high glass transition temperature Tg necessitate modification of the PLLA to improve its application efficacy in physiological conditions. This study proposed to modify PLLA by blending it with a biodegradable poly(3-hydroxybutyrate-co-3-hydroxyv alerate) (PHBV) for fabricating fibrous PLLA/PHBV scaffold via electrospinning. Different polymer solutions at the concentration of 10 wt% are prepared by dissolving PLLA/PHBV blends at varying ratios in a solvent mixture of chloroform/N,Ndimethylformamide (9:1 in volume). Thereafter, these polymer solutions are electrospun into PLLA/PHBV composite fibers and characterizd by different techniques. Finally, cytocompability of the fibrous PLLA/PHBV scaffolds are evaluated by culturing bone marrow stem cells (BMSCs) seeded at different densities onto them for cell proliferation assay. The results show that ultrafine fibers of PLLA/PHBV with an averged diameter of ca. 3 μm can be successfully fabricated
Fig. 1. Illustration of charge-conversional polyprodrug amphiphiles, P(DMA-co-TPAMA/ FITC)-b-PCPTMA, for intracellular dual-responsive drug delivery.
Keywords: charge-conversional, polyprodrug amphiphiles, dual-responsive, drug delivery Acknowledgements This work was supported by the National Natural Scientific Foundation of China (NNSFC) Project (51403042 and 51033005), the
Fig. 1. (a) Tg decreases with increasing the loading ratio of PHBV in the PLLA/PHBV composite fibers. (b) Demonstrattion of shape memory effect of the electrospun PLLA/ PHBV (7:3) fiber mat. (c) Proliferation data of BMSCs cultured on the fibrous PLLA/ PHBV scaffolds.
Abstracts / Journal of Controlled Release 259 (2017) e5–e195
through electrospinning. Incorporation of PHBV gives rise to significantly improved mechanical properties. Tg of the composite fibers decreases with increasing the PHBV loading ratio (Fig. 1a). Excellent shape memory properties with high shape fixing ratio (N98%) and shape recovery ratio (N96%) are observed and macroscopically demonstratged (Fig. 1b). Moreover, in comparison with the neat PLLA and PHBV fibrous scaffolds, the fibrous scaffolds of PLLA/PHBV are able to promote the BMSCs to grow better (Fig. 1c). These attractive results warrant further investigation in vitro and in vivo on the feasibility of applying the biomimicking fibrous PLLA/PHBV scaffold with shape memory effect for tissue engineering applications.
e145
IR-780, was capable of flowing at body temperature. We demonstrated that the NIR irradiation of the nanoparticles for short-time led to rapid DOX release from the hydrophobic flow cores, achieving NIR-activated super-sensitive drug release inside tumor cells, which in turn facilitated the overcoming of DOX resistance of cancer cells in vitro and in vivo.
Keywords: shape memory polymer, PLLA, PHBV, electrospinning, Tg, tissue engineering Acknowledgements The authors are grateful for the financial support from the Key Project of Science and Technology of Shanghai Municipality (14JC1490100), and the National Natural Science Foundation of China (51073032, 31570969). Reference [1] Y.S Wong, S.S Venkatraman, Recovery as a measure of oriented crystalline structure in poly(L-lactide) used as shape memory polymer, Acta Mater. 58 (2010) 49-58.
Fig. 1. Schematic illustration of the NIR-activated drug release from polymeric nanocarriers with flow core (A) or rigid core (B) at body temperature.
doi:10.1016/j.jconrel.2017.03.292 Keywords: photoactivation, NIR-responsive nanomaterials, photothermal therapy, super-sensitive drug release, cancer therapy Near infrared light-activated super-sensitive drug release using nanoparticles with a flow core
Acknowledgements The authors are grateful for the financial support from the National Natural Science Foundation of China (51473043).
Jun-Xia Wang, Xian-Zhu Yang⁎ School of Biological and Medical Engineering, Hefei University of Technology, Hefei 230009, China ⁎Corresponding author. E-mail address: [email protected] (X.-Z. Yang)
[1] V. Shanmugam, S. Selvakumar, C. S. Yeh, Near-infrared light-responsive nanomaterials in cancer therapeutics. Chem. Soc. Rev. 43 (2014) 6254-6287.
Photoactivated nanomaterials exhibit immense promise for biomedical applications because noninvasive light stimulus can be spatially and temporally controlled, resulting in great safety, specificity, and efficacy. Specifically, near infrared (NIR) light radiation has an effective penetration depth and is less attenuated in biological tissues. Thus, NIRsensitive nanomaterials are of particular interest in the delivery of active substances to cells or tissues [1]. The NIR irradiation generates heat by the photothermal effect of encapsulated photothermal agents, and the heat can promote drug release from the hydrophobic cores of polymeric nanoparticles. However, the most widely used biodegradable materials (i.e., poly(d,l-lactide) (PLA), poly(lactide-co-glycotide) (PLGA) and poly(ε-caprolactone) (PCL)) have high glass-transition temperatures or melting temperatures, and thus rigid chains inside nanoparticles. The rigid cores may hinder the chain motion relative to each other during photothermal conversion processes that limit the diffusion of drug molecules. Thus, these types of materials are not ideal core materials for use in NIR-induced drug release for cancer therapy. The entire molecular motions of polymers are known to be activated in viscous flow states. Therefore, if polymeric nanoparticles possess flowable cores, NIR-activated super-sensitive drug release can be expected. Herein, we report on the NIR-activated super-sensitive drug release from polyphosphoester-based nanoparticles. As shown in Fig. 1, an amphiphilic block copolymer of PEG and poly(2-hexoxy-2-oxo-1,3,2dioxaphospholane) (PHEP) was formulated into nanoparticles. The flexible chain PHEP, which formed the nanoparticular core to encapsulate a model chemodrug DOX and the NIR photothermal agent
Reference
doi:10.1016/j.jconrel.2017.03.293
Multifunctional nanoparticles combining host-guest interaction of CB[7] and AuNS for light-promoted endosome escape and high gene transfection Jianwei Du, Xiao Zhao, Youxiang Wang⁎ MOE Key Laboratory of Macromolecular Synthesis and Functionalization, Department of Polymer Science and Engineering, Zhejiang University, Hangzhou 310027, China ⁎Corresponding author. E-mail addresses: [email protected] (J. Du), [email protected] (Y. Wang) Cucurbit[7]uril (CB[7]), an important member of cucurbit[n]uril could form inclusion complexes with many guest molecules such as adamantane, viologen and naphthalene derivatives [1, 2]. Furthermore, it was very interesting to find that CB[7] could self-assemble on photo-thermal gold nanoparticles [3]. Thus, by combining hostguest interaction of CB[7] and gold nanosphere (AuNS), an easy strategy for ligand modification was designed (Fig. 1). In this work, we successfully synthesized methyl viologen modified polyethylenimine (Mv-S-S-PEI, MP) and naphthalene modified polyethyleneglycol (Np-CH=N-PEG, NP) via pH- and GSH-responsive bonds, respectively (1H NMR). Then, the ternary complex MP@CB[7]@NP was formed by host-guest interacting with CB[7]