- Email: [email protected]
PLK1shRNA and doxorubicin co-loaded thermosensitive PLGA–PEG–PLGA hydrogels for localized and combined treatment of human osteosarcoma
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Abstracts / Journal of Controlled Release 213 (2015) e8–e152
Keywords: stem cells, disulfide-based polyurethane, human primary cells, gene transfection Acknowledgment This work was financially supported by the Ministry of Science and Technology of China (2014CB964600, 2012CB966300), the National Natural Science Foundation of China (20904041, 81271369), and the Shanghai Municipal Natural Science Foundation (13ZR1443600). References [1] H.K. Salem, C. Thiemermann, Mesenchymal stromal cells: current understanding and clinical status, Stem Cells 28 (2010) 585–596. [2] J.L. Santos, D. Pandita, J. Rodrigues, A.P. Pego, P.L. Granja, H. Tomas, Non-viral gene delivery to mesenchymal stem cells: methods, strategies and application in bone tissue engineering and regeneration, Curr. Gene Ther. 11 (2011) 46–57. [3] C.E. Thomas, A. Ehrhardt, M.A. Kay, Progress and problems with the use of viral vectors for gene therapy, Nat. Rev. Genet. 4 (2003) 346–358.
doi:10.1016/j.jconrel.2015.05.025
PLK1shRNA and doxorubicin co-loaded thermosensitive PLGA–PEG–PLGA hydrogels for localized and combined treatment of human osteosarcoma Chaoliang Hea,*, Hecheng Maa,b, Yilong Chenga, Dongsong Lib, Yubao Gongb, Jianguo Liub,*, Huayu Tiana,*, Xuesi Chena a Key Laboratory of Polymer Ecomaterials, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun 130022, China b Department of Orthopaedics, The First Hospital of Jilin University, Jilin University, Changchun 130021, China ⁎Corresponding authors. E-mail addresses: [email protected] (C. He), [email protected] (J. Liu), [email protected] (H. Tian).
Fig. 1. Schematic illustration for the synergistic effect of PLK1shRNA/PEI-Lys and DOX⋅HCl co-loaded hydrogel on localized tumor treatment.
tumor apoptosis, and enhanced expression of apoptosis-related genes and cell cycle regulation. Furthermore, ex vivo histological analysis of main organs of the treated mice suggested lower systemic toxicity of the hydrogel treatments. Therefore, the localized and sustained codelivery of PLK1shRNA and DOX by the biodegradable injectable hydrogel may be a promising strategy for osteosarcoma treatment. Keywords: combination therapy, PLK1 silencing, sustained delivery, injectable hydrogel References [1] A. Luetke, P.A. Meyers, I. Lewis, H. Juergens, Osteosarcoma treatment — Where do we stand? A state of the art review, Cancer Treat. Rev. 40 (2014) 523–532. [2] C. He, S.W. Kim, D.S. Lee, In situ gelling stimuli-sensitive block copolymer hydrogels for drug delivery, J. Control. Release 127 (2008) 189–207. [3] L. Yu, J. Ding, Injectable hydrogels as unique biomedical materials, Chem. Soc. Rev. 37 (2008) 1473–1481.
doi:10.1016/j.jconrel.2015.05.026
A directional liquid-transfer nonwoven for skin tissue engineering Osteosarcoma is a common malignant bone cancer in children and adolescents. In modern treatments, different chemotherapeutic drugs are administered combined either intravenously or orally both before and after surgery [1]. Doxorubicin⋅hydrochloride (DOX⋅HCl), a broad-spectrum anti-tumor drug, has shown to be effective in osteosarcoma treatment. Additionally, gene therapy has been an emerging targeted therapeutic strategy for osteosarcoma treatment. For instance, polo-like kinase 1 (PLK1) gene has been chosen as a promising therapeutic target for osteosarcoma therapy, due to its involvement in carcinogenesis. Nevertheless, reports on the codelivery of anti-tumor drugs and genes for combination cancer treatment through a localized and sustained strategy, such as by using biodegradable and injectable hydrogels, are still limited to-date [2,3]. In this study, we present a novel strategy by localized and sustained co-delivery of PLK1shRNA/lysine-modified PEI complexes (PLK1shRNA/PEI-Lys) and DOX⋅HCl using a biodegradable and thermosensitive PLGA–PEG–PLGA hydrogel for osteosarcoma treatment (Fig. 1). The cell culture studies showed that PLK1shRNA/PEILys and DOX co-loaded hydrogels exhibited synergistic effect to osteosarcoma Saos-2 and MG-63 cells in vitro. The subcutaneous injection of the hydrogels beside the tumors of nude mice bearing osteosarcoma Saos-2 xenografts showed that these hydrogels induced synergistic anti-tumor efficacy in vivo. The combination treatment was found to lead to almost complete suppression of tumor growth up to 16 days, increased PLK1 silencing, increased
Chen Huang*, Haoxuan Li, Dawei Li, Yu Song Key Laboratory of Textile Science & Technology, Ministry of Education, College of Textiles, Donghua University, Shanghai 201620, China ⁎Corresponding author. E-mail address: [email protected] (C. Huang). Directional liquid-transfer is imperative to various physiological functions and physical processes [1]. It has been verified that, in a fibrous system, directional water-transfer can be achieved through a gradient wettability without applying any external forces, thus making the process energy efficient and easy to be incorporated into advanced fabrics [2]. In the present study, we report the directional liquid-transfer in a nonwoven composite via spunlacing technology. The nonwoven are composed of two fibrous layers. The upper layer is formed by hydrophobic chitosan fibers (Fig. 1a, white arrow) for its widely reported biocompatibility and antibacterial properties, while hydrophilic viscose fibers (Fig. 1a, yellow arrow) were selected as the lower layer to create a cross-sectional wettability gradient. Induced by the gradient, water droplets can flow easily from the chitosan side to viscose side, whereas they are blocked when penetrating from the reverse direction (Fig. 1b). To demonstrate the biosafety of the nonwoven, a typical cytotoxicity test (according to DS/EN ISO10993-5) was implemented with rat dermal fibroblasts. Fibroblasts were found to grow and elongate along the axis of chitosan fibers. After 5 days of culture, all fibers were
Abstracts / Journal of Controlled Release 213 (2015) e8–e152
Keywords: stem cells, disulfide-based polyurethane, human primary cells, gene transfection Acknowledgment This work was financially supported by the Ministry of Science and Technology of China (2014CB964600, 2012CB966300), the National Natural Science Foundation of China (20904041, 81271369), and the Shanghai Municipal Natural Science Foundation (13ZR1443600). References [1] H.K. Salem, C. Thiemermann, Mesenchymal stromal cells: current understanding and clinical status, Stem Cells 28 (2010) 585–596. [2] J.L. Santos, D. Pandita, J. Rodrigues, A.P. Pego, P.L. Granja, H. Tomas, Non-viral gene delivery to mesenchymal stem cells: methods, strategies and application in bone tissue engineering and regeneration, Curr. Gene Ther. 11 (2011) 46–57. [3] C.E. Thomas, A. Ehrhardt, M.A. Kay, Progress and problems with the use of viral vectors for gene therapy, Nat. Rev. Genet. 4 (2003) 346–358.
doi:10.1016/j.jconrel.2015.05.025
PLK1shRNA and doxorubicin co-loaded thermosensitive PLGA–PEG–PLGA hydrogels for localized and combined treatment of human osteosarcoma Chaoliang Hea,*, Hecheng Maa,b, Yilong Chenga, Dongsong Lib, Yubao Gongb, Jianguo Liub,*, Huayu Tiana,*, Xuesi Chena a Key Laboratory of Polymer Ecomaterials, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun 130022, China b Department of Orthopaedics, The First Hospital of Jilin University, Jilin University, Changchun 130021, China ⁎Corresponding authors. E-mail addresses: [email protected] (C. He), [email protected] (J. Liu), [email protected] (H. Tian).
Fig. 1. Schematic illustration for the synergistic effect of PLK1shRNA/PEI-Lys and DOX⋅HCl co-loaded hydrogel on localized tumor treatment.
tumor apoptosis, and enhanced expression of apoptosis-related genes and cell cycle regulation. Furthermore, ex vivo histological analysis of main organs of the treated mice suggested lower systemic toxicity of the hydrogel treatments. Therefore, the localized and sustained codelivery of PLK1shRNA and DOX by the biodegradable injectable hydrogel may be a promising strategy for osteosarcoma treatment. Keywords: combination therapy, PLK1 silencing, sustained delivery, injectable hydrogel References [1] A. Luetke, P.A. Meyers, I. Lewis, H. Juergens, Osteosarcoma treatment — Where do we stand? A state of the art review, Cancer Treat. Rev. 40 (2014) 523–532. [2] C. He, S.W. Kim, D.S. Lee, In situ gelling stimuli-sensitive block copolymer hydrogels for drug delivery, J. Control. Release 127 (2008) 189–207. [3] L. Yu, J. Ding, Injectable hydrogels as unique biomedical materials, Chem. Soc. Rev. 37 (2008) 1473–1481.
doi:10.1016/j.jconrel.2015.05.026
A directional liquid-transfer nonwoven for skin tissue engineering Osteosarcoma is a common malignant bone cancer in children and adolescents. In modern treatments, different chemotherapeutic drugs are administered combined either intravenously or orally both before and after surgery [1]. Doxorubicin⋅hydrochloride (DOX⋅HCl), a broad-spectrum anti-tumor drug, has shown to be effective in osteosarcoma treatment. Additionally, gene therapy has been an emerging targeted therapeutic strategy for osteosarcoma treatment. For instance, polo-like kinase 1 (PLK1) gene has been chosen as a promising therapeutic target for osteosarcoma therapy, due to its involvement in carcinogenesis. Nevertheless, reports on the codelivery of anti-tumor drugs and genes for combination cancer treatment through a localized and sustained strategy, such as by using biodegradable and injectable hydrogels, are still limited to-date [2,3]. In this study, we present a novel strategy by localized and sustained co-delivery of PLK1shRNA/lysine-modified PEI complexes (PLK1shRNA/PEI-Lys) and DOX⋅HCl using a biodegradable and thermosensitive PLGA–PEG–PLGA hydrogel for osteosarcoma treatment (Fig. 1). The cell culture studies showed that PLK1shRNA/PEILys and DOX co-loaded hydrogels exhibited synergistic effect to osteosarcoma Saos-2 and MG-63 cells in vitro. The subcutaneous injection of the hydrogels beside the tumors of nude mice bearing osteosarcoma Saos-2 xenografts showed that these hydrogels induced synergistic anti-tumor efficacy in vivo. The combination treatment was found to lead to almost complete suppression of tumor growth up to 16 days, increased PLK1 silencing, increased
Chen Huang*, Haoxuan Li, Dawei Li, Yu Song Key Laboratory of Textile Science & Technology, Ministry of Education, College of Textiles, Donghua University, Shanghai 201620, China ⁎Corresponding author. E-mail address: [email protected] (C. Huang). Directional liquid-transfer is imperative to various physiological functions and physical processes [1]. It has been verified that, in a fibrous system, directional water-transfer can be achieved through a gradient wettability without applying any external forces, thus making the process energy efficient and easy to be incorporated into advanced fabrics [2]. In the present study, we report the directional liquid-transfer in a nonwoven composite via spunlacing technology. The nonwoven are composed of two fibrous layers. The upper layer is formed by hydrophobic chitosan fibers (Fig. 1a, white arrow) for its widely reported biocompatibility and antibacterial properties, while hydrophilic viscose fibers (Fig. 1a, yellow arrow) were selected as the lower layer to create a cross-sectional wettability gradient. Induced by the gradient, water droplets can flow easily from the chitosan side to viscose side, whereas they are blocked when penetrating from the reverse direction (Fig. 1b). To demonstrate the biosafety of the nonwoven, a typical cytotoxicity test (according to DS/EN ISO10993-5) was implemented with rat dermal fibroblasts. Fibroblasts were found to grow and elongate along the axis of chitosan fibers. After 5 days of culture, all fibers were