pH-Responsive Artesunate Polymer Prodrugs with Enhanced Ablation Effect on Rodent Xenograft Colon Cancer
Dan-Li Hao, Ran Xie, Ge-Jing De, Hong Yi, Chen Zang, Mi-Yi Yang, Li Liu, Hai Ma, Wei-Yan Cai, Qing-He Zhao, Feng Sui, Yan-Jun Chen Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing 100700, People’s Republic of ChinaCorrespondence: Qing-He Zhao; Yan-Jun...
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Dove Medical Press
2020
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oai:doaj.org-article:4bdfa964c95744eea285336c8d5f18f42021-12-02T10:17:24ZpH-Responsive Artesunate Polymer Prodrugs with Enhanced Ablation Effect on Rodent Xenograft Colon Cancer1178-2013https://doaj.org/article/4bdfa964c95744eea285336c8d5f18f42020-03-01T00:00:00Zhttps://www.dovepress.com/ph-responsive-artesunate-polymer-prodrugs-with-enhanced-ablation-effec-peer-reviewed-article-IJNhttps://doaj.org/toc/1178-2013Dan-Li Hao, Ran Xie, Ge-Jing De, Hong Yi, Chen Zang, Mi-Yi Yang, Li Liu, Hai Ma, Wei-Yan Cai, Qing-He Zhao, Feng Sui, Yan-Jun Chen Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing 100700, People’s Republic of ChinaCorrespondence: Qing-He Zhao; Yan-Jun Chen Tel/ Fax +86-10-84036059Email qhzhao@icmm.ac.cn; yjchen@icmm.ac.cnPurpose: In this study, pH-sensitive poly(2-ethyl-2-oxazoline)-poly(lactic acid)-poly(β-amino ester) (PEOz-PLA-PBAE) triblock copolymers were synthesized and were conjugated with an antimalaria drug artesunate (ART), for inhibition of a colon cancer xenograft model.Methods: The as-prepared polymer prodrugs are tended to self-assemble into polymeric micelles in aqueous milieu, with PEOz segment as hydrophilic shell and PLA-PBAE segment as hydrophobic core.Results: The pH sensitivity of the as-prepared copolymers was confirmed by acid-base titration with pKb values around 6.5. The drug-conjugated polymer micelles showed high stability for at least 96 h in PBS and 37°C, respectively. The as-prepared copolymer prodrugs showed high drug loading content, with 9.57%± 1.24% of drug loading for PEOz-PLA-PBAE-ART4. The conjugated ART could be released in a sustained and pH-dependent manner, with 92% of released drug at pH 6.0 and 57% of drug released at pH 7.4, respectively. In addition, in vitro experiments showed higher inhibitory effect of the prodrugs on rodent CT-26 cells than that of free ART. Animal studies also demonstrated the enhanced inhibitory efficacy of PEOz-PLA-PBAE-ART2 micelles on the growth of rodent xenograft tumor.Conclusion: The pH-responsive artesunate polymer prodrugs are promising candidates for colon cancer adjuvant therapy.Keywords: artesunate, micelles, pH responsive, polymer prodrug, poly(2-ethyl-2-oxazoline), poly(β-amino ester)Hao DLXie RDe GJYi HZang CYang MYLiu LMa HCai WYZhao QHSui FChen YJDove Medical Pressarticleartesunatemicellesph responsivepolymer prodrugpoly(2-ethyl-2-oxazoline)poly(β-amino ester)Medicine (General)R5-920ENInternational Journal of Nanomedicine, Vol Volume 15, Pp 1771-1786 (2020) |
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| topic |
artesunate micelles ph responsive polymer prodrug poly(2-ethyl-2-oxazoline) poly(β-amino ester) Medicine (General) R5-920 |
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artesunate micelles ph responsive polymer prodrug poly(2-ethyl-2-oxazoline) poly(β-amino ester) Medicine (General) R5-920 Hao DL Xie R De GJ Yi H Zang C Yang MY Liu L Ma H Cai WY Zhao QH Sui F Chen YJ pH-Responsive Artesunate Polymer Prodrugs with Enhanced Ablation Effect on Rodent Xenograft Colon Cancer |
| description |
Dan-Li Hao, Ran Xie, Ge-Jing De, Hong Yi, Chen Zang, Mi-Yi Yang, Li Liu, Hai Ma, Wei-Yan Cai, Qing-He Zhao, Feng Sui, Yan-Jun Chen Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing 100700, People’s Republic of ChinaCorrespondence: Qing-He Zhao; Yan-Jun Chen Tel/ Fax +86-10-84036059Email qhzhao@icmm.ac.cn; yjchen@icmm.ac.cnPurpose: In this study, pH-sensitive poly(2-ethyl-2-oxazoline)-poly(lactic acid)-poly(β-amino ester) (PEOz-PLA-PBAE) triblock copolymers were synthesized and were conjugated with an antimalaria drug artesunate (ART), for inhibition of a colon cancer xenograft model.Methods: The as-prepared polymer prodrugs are tended to self-assemble into polymeric micelles in aqueous milieu, with PEOz segment as hydrophilic shell and PLA-PBAE segment as hydrophobic core.Results: The pH sensitivity of the as-prepared copolymers was confirmed by acid-base titration with pKb values around 6.5. The drug-conjugated polymer micelles showed high stability for at least 96 h in PBS and 37°C, respectively. The as-prepared copolymer prodrugs showed high drug loading content, with 9.57%± 1.24% of drug loading for PEOz-PLA-PBAE-ART4. The conjugated ART could be released in a sustained and pH-dependent manner, with 92% of released drug at pH 6.0 and 57% of drug released at pH 7.4, respectively. In addition, in vitro experiments showed higher inhibitory effect of the prodrugs on rodent CT-26 cells than that of free ART. Animal studies also demonstrated the enhanced inhibitory efficacy of PEOz-PLA-PBAE-ART2 micelles on the growth of rodent xenograft tumor.Conclusion: The pH-responsive artesunate polymer prodrugs are promising candidates for colon cancer adjuvant therapy.Keywords: artesunate, micelles, pH responsive, polymer prodrug, poly(2-ethyl-2-oxazoline), poly(β-amino ester) |
| format |
article |
| author |
Hao DL Xie R De GJ Yi H Zang C Yang MY Liu L Ma H Cai WY Zhao QH Sui F Chen YJ |
| author_facet |
Hao DL Xie R De GJ Yi H Zang C Yang MY Liu L Ma H Cai WY Zhao QH Sui F Chen YJ |
| author_sort |
Hao DL |
| title |
pH-Responsive Artesunate Polymer Prodrugs with Enhanced Ablation Effect on Rodent Xenograft Colon Cancer |
| title_short |
pH-Responsive Artesunate Polymer Prodrugs with Enhanced Ablation Effect on Rodent Xenograft Colon Cancer |
| title_full |
pH-Responsive Artesunate Polymer Prodrugs with Enhanced Ablation Effect on Rodent Xenograft Colon Cancer |
| title_fullStr |
pH-Responsive Artesunate Polymer Prodrugs with Enhanced Ablation Effect on Rodent Xenograft Colon Cancer |
| title_full_unstemmed |
pH-Responsive Artesunate Polymer Prodrugs with Enhanced Ablation Effect on Rodent Xenograft Colon Cancer |
| title_sort |
ph-responsive artesunate polymer prodrugs with enhanced ablation effect on rodent xenograft colon cancer |
| publisher |
Dove Medical Press |
| publishDate |
2020 |
| url |
https://doaj.org/article/4bdfa964c95744eea285336c8d5f18f4 |
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