pH-Responsive Artesunate Polymer Prodrugs with Enhanced Ablation Effect on Rodent Xenograft Colon Cancer
Authors: Chen Zang
Ran Xie
Hong Yi
Feng Sui
Li Liu
Hai Ma
Qing-He Zhao
Mi-Yi Yang
Dan-Li Hao
Wei-Yan Cai
Yan-Jun Chen
Ge-Jing De
Journal: International Journal of Nanomedicine (2020)
Discipline: PHARMACOLOGY & TOXICOLOGY
Keywords: artesunate; micelles; pH responsive; poly(2-ethyl-2-oxazoline); poly(β-amino ester)
Affiliations: Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing 100700, People's Republic of China.

Abstract:  Purpose: 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. 

Retracted: No

PubPeer comments:
 Figure 1A appears to have some repeated images. *** ![file] , 
 Thank you very much for your timely suggestions, we pasted the same images when preparing our manuscripts, we would be in contact with the editorail to make a revision. Thanks again and best. , 
 CORRIGENDUM Hao DL, Xie R, De GJ, et al. Int J Nanomed. 2020;15:1771u2013 1786. The authors have advised due to an error that occurred inadvertently at the time of figure assembly, the images of the cellular uptake of free C6 and ART-M1-C6 are incorrect for Figure 1 on page 1780. The authors have also advised on page 1779, Cytotoxicity Assay and Cellular Apoptosis Analysis section, second paragraph, the text u201cThe apoptosis rates for cells treated with free ART, PBAE-ART4 and PBAE-ART2 for 24 h were 8.76%, 11.88% and 14.27%, respectively. After incubation for 72 h, the apoptosis rates were increased to 18.41%, 22.49% and 26.85%, respectively, with stronger apoptosis rates were observed in the micelles groups than that of free drug (Figure 2)u201d should read u201cThe apoptosis rates for cells treated with free ART, PBAE-ART4 and PBAE-ART2 for 24 h were 8.73%, 11.84% and 14.23%, respectively. After incubation for 72 h, the apoptosis rates were increased to 18.35%, 22.42% and 26.76%, respectively, with stronger apoptosis rates were observed in the micelles groups than that of free drug (Figure 2).u201d The authors also advised that there is an error in Figure S2 of the supplementary material, the images of the CMC of PEOz-PLA-PBAE-2 and PEOz-PLA-PBAE-3 should be interchanged. The authors apologize for these errors and advise they do not affect the results and conclusions of the paper. More at link: https: www.dovepress.com corrigendum-ph-responsive-artesunate-polymer-prodrugs-with-enhanced-ab-peer-reviewed-fulltext-article-IJN ![file] ,