D-α-tocopherol polyethylene glycol 1000 succinate-modified liposomes with an siRNA corona confer enhanced cellular uptake and targeted delivery of doxorubicin via tumor priming
Xi Tan,1,* Yan Fang,1,* Yuanyuan Ren,1 Yinghuan Li,2 Peicheng Wu,3 Xiangliang Yang,1,4 Wei Liu1,4 1College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan 430074, People’s Republic of China; 2School of Pharmaceutical Sciences, Beijing Area Major Labora...
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Dove Medical Press
2019
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oai:doaj.org-article:94a1858bf1114b95a9d510b9f7f6d93a2021-12-02T04:33:44ZD-α-tocopherol polyethylene glycol 1000 succinate-modified liposomes with an siRNA corona confer enhanced cellular uptake and targeted delivery of doxorubicin via tumor priming1178-2013https://doaj.org/article/94a1858bf1114b95a9d510b9f7f6d93a2019-02-01T00:00:00Zhttps://www.dovepress.com/d-alpha-tocopherol-polyethylene-glycol-1000-succinate-modified-liposom-peer-reviewed-article-IJNhttps://doaj.org/toc/1178-2013Xi Tan,1,* Yan Fang,1,* Yuanyuan Ren,1 Yinghuan Li,2 Peicheng Wu,3 Xiangliang Yang,1,4 Wei Liu1,4 1College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan 430074, People’s Republic of China; 2School of Pharmaceutical Sciences, Beijing Area Major Laboratory of Peptide and Small Molecular Drugs, Engineering Research Center of Endogenous Prophylactic of Ministry of Education of China, Capital Medical University, Beijing 100069, People’s Republic of China; 3School of Biosciences and Biopharmaceuticals, Institute of Biopharmaceuticals, Guangdong Pharmaceutical University, Guangzhou 510006, People’s Republic of China; 4National Engineering Research Center for Nanomedicine, Huazhong University of Science and Technology, Wuhan 430074, People’s Republic of China *These authors contributed equally to this work Background: Combination therapy employing siRNAs and antitumor drugs is a promising method for the treatment of solid tumors. However, regarding combined treatments involving siRNAs and chemotherapeutic reagents, most prior research has focused on the enhanced cytotoxicity against tumor cells conferred by downregulation of the targeted protein. Purpose: We developed D-α-tocopherol polyethylene glycol 1000 succinate (TPGS)-modified cationic liposomes (LPs) to simultaneously deliver doxorubicin (Dox) and the Bcl-2 siRNA (siBcl-2) for synergistic chemotherapy. The co-loading of siBcl-2 onto the Dox-loaded cationic LPs (siBcl-2/Dox-TPGS-LPs) could promote cellular uptake, cytotoxicity against 3D H22 tumor spheroids, circulation in the blood, drug accumulation at tumor sites, and synergistic chemotherapy in vivo. Methods: The siBcl-2/Dox-TPGS-LPs were constructed by co-loading siBcl-2 onto the Dox-loaded TPGS-modified cationic LPs (Dox-TPGS-LPs), and Dox entrapment into the LPs was achieved using an ammonium sulfate gradient method. The antitumor effects of siBcl-2/Dox-TPGS-LPs were studied in murine hepatic carcinoma H22 cells, 3D H22 tumor spheroids, and H22 tumor-bearing mice. Results: Dynamic light scattering technique and transmission electron microscopy images revealed that siBcl-2 loaded onto the Dox-TPGS-LPs formed a prominent corona at an nitrogen to phosphorus (N/P) ratio of 4:1, resulting in particle size increase from 155 to 210 nm and a weak positive zeta potential (+12.5 mV). The siBcl-2/Dox-TPGS-LPs enhanced the cellular uptake of Dox, promoted toxicity against 3D H22 tumor spheroids via tumor priming, prolonged Dox circulation in the blood, and increased accumulation of Dox at tumor sites, thereby enhancing the cytotoxicity of Dox in vitro and its chemotherapeutic efficacy in vivo. Conclusion: The siBcl-2/Dox-TPGS-LPs demonstrated a strong potential for application in synergistic chemotherapy. The co-loading of siRNAs both sensitized cells toward antitumor drugs by downregulating the expression level of a specific protein and influenced the pharmacokinetic behavior of the co-delivery system in vitro and in vivo. Keywords: siRNA corona, cationic liposomes, co-delivery, Bcl-2, tumor priming, synergistic chemotherapyTan XFang YRen YLi YWu PYang XLiu WDove Medical PressarticlesiRNA coronacationic liposomesco-deliveryBcl-2tumor primingsynergistic chemotherapyMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol Volume 14, Pp 1255-1268 (2019) |
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DOAJ |
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siRNA corona cationic liposomes co-delivery Bcl-2 tumor priming synergistic chemotherapy Medicine (General) R5-920 |
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siRNA corona cationic liposomes co-delivery Bcl-2 tumor priming synergistic chemotherapy Medicine (General) R5-920 Tan X Fang Y Ren Y Li Y Wu P Yang X Liu W D-α-tocopherol polyethylene glycol 1000 succinate-modified liposomes with an siRNA corona confer enhanced cellular uptake and targeted delivery of doxorubicin via tumor priming |
| description |
Xi Tan,1,* Yan Fang,1,* Yuanyuan Ren,1 Yinghuan Li,2 Peicheng Wu,3 Xiangliang Yang,1,4 Wei Liu1,4 1College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan 430074, People’s Republic of China; 2School of Pharmaceutical Sciences, Beijing Area Major Laboratory of Peptide and Small Molecular Drugs, Engineering Research Center of Endogenous Prophylactic of Ministry of Education of China, Capital Medical University, Beijing 100069, People’s Republic of China; 3School of Biosciences and Biopharmaceuticals, Institute of Biopharmaceuticals, Guangdong Pharmaceutical University, Guangzhou 510006, People’s Republic of China; 4National Engineering Research Center for Nanomedicine, Huazhong University of Science and Technology, Wuhan 430074, People’s Republic of China *These authors contributed equally to this work Background: Combination therapy employing siRNAs and antitumor drugs is a promising method for the treatment of solid tumors. However, regarding combined treatments involving siRNAs and chemotherapeutic reagents, most prior research has focused on the enhanced cytotoxicity against tumor cells conferred by downregulation of the targeted protein. Purpose: We developed D-α-tocopherol polyethylene glycol 1000 succinate (TPGS)-modified cationic liposomes (LPs) to simultaneously deliver doxorubicin (Dox) and the Bcl-2 siRNA (siBcl-2) for synergistic chemotherapy. The co-loading of siBcl-2 onto the Dox-loaded cationic LPs (siBcl-2/Dox-TPGS-LPs) could promote cellular uptake, cytotoxicity against 3D H22 tumor spheroids, circulation in the blood, drug accumulation at tumor sites, and synergistic chemotherapy in vivo. Methods: The siBcl-2/Dox-TPGS-LPs were constructed by co-loading siBcl-2 onto the Dox-loaded TPGS-modified cationic LPs (Dox-TPGS-LPs), and Dox entrapment into the LPs was achieved using an ammonium sulfate gradient method. The antitumor effects of siBcl-2/Dox-TPGS-LPs were studied in murine hepatic carcinoma H22 cells, 3D H22 tumor spheroids, and H22 tumor-bearing mice. Results: Dynamic light scattering technique and transmission electron microscopy images revealed that siBcl-2 loaded onto the Dox-TPGS-LPs formed a prominent corona at an nitrogen to phosphorus (N/P) ratio of 4:1, resulting in particle size increase from 155 to 210 nm and a weak positive zeta potential (+12.5 mV). The siBcl-2/Dox-TPGS-LPs enhanced the cellular uptake of Dox, promoted toxicity against 3D H22 tumor spheroids via tumor priming, prolonged Dox circulation in the blood, and increased accumulation of Dox at tumor sites, thereby enhancing the cytotoxicity of Dox in vitro and its chemotherapeutic efficacy in vivo. Conclusion: The siBcl-2/Dox-TPGS-LPs demonstrated a strong potential for application in synergistic chemotherapy. The co-loading of siRNAs both sensitized cells toward antitumor drugs by downregulating the expression level of a specific protein and influenced the pharmacokinetic behavior of the co-delivery system in vitro and in vivo. Keywords: siRNA corona, cationic liposomes, co-delivery, Bcl-2, tumor priming, synergistic chemotherapy |
| format |
article |
| author |
Tan X Fang Y Ren Y Li Y Wu P Yang X Liu W |
| author_facet |
Tan X Fang Y Ren Y Li Y Wu P Yang X Liu W |
| author_sort |
Tan X |
| title |
D-α-tocopherol polyethylene glycol 1000 succinate-modified liposomes with an siRNA corona confer enhanced cellular uptake and targeted delivery of doxorubicin via tumor priming |
| title_short |
D-α-tocopherol polyethylene glycol 1000 succinate-modified liposomes with an siRNA corona confer enhanced cellular uptake and targeted delivery of doxorubicin via tumor priming |
| title_full |
D-α-tocopherol polyethylene glycol 1000 succinate-modified liposomes with an siRNA corona confer enhanced cellular uptake and targeted delivery of doxorubicin via tumor priming |
| title_fullStr |
D-α-tocopherol polyethylene glycol 1000 succinate-modified liposomes with an siRNA corona confer enhanced cellular uptake and targeted delivery of doxorubicin via tumor priming |
| title_full_unstemmed |
D-α-tocopherol polyethylene glycol 1000 succinate-modified liposomes with an siRNA corona confer enhanced cellular uptake and targeted delivery of doxorubicin via tumor priming |
| title_sort |
d-α-tocopherol polyethylene glycol 1000 succinate-modified liposomes with an sirna corona confer enhanced cellular uptake and targeted delivery of doxorubicin via tumor priming |
| publisher |
Dove Medical Press |
| publishDate |
2019 |
| url |
https://doaj.org/article/94a1858bf1114b95a9d510b9f7f6d93a |
| work_keys_str_mv |
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