title: Novel multiarm polyethylene glycol-dihydroartemisinin conjugates enhancing therapeutic efficacy in non-small-cell lung cancer.
abstract: The clinical application of dihydroartemisinin (DHA) has been hampered due to its poor water-solubility. To overcome this hurdle, we devised a novel polymer-drug conjugate, multiarm polyethylene glycol-dihydroartemisinin (PEG-DHA), made by linking DHA with multiarm polyethylene glycol. Herein, we investigated PEG-DHA on chemical structure, hydrolysis, solubility, hemolysis, cell cytotoxicity in vitro, and efficacy in vivo. The PEG-DHA conjugates have showed moderate drug loadings (2.82 ~ 8.14 wt%), significantly good water-solubilities (82- ~ 163-fold of DHA), excellent in vitro anticancer activities (at concentrations ≥8 μg/ml, showed only 15-20% cell viability) with potency similar to that of native DHA, and long blood circulation half-time (5.75- ~ 16.75-fold of DHA). Subsequent tumor xenograft assays demonstrated a superior therapeutic effect of PEG-DHA on inhibition of tumor growth compared with native DHA. The novel PEG-DHA conjugates can not only improve the solubility and efficacy of DHA but also show the potential of scale-up production and clinical application.
authors: MOE Key Laboratory of Wooden Material Science and Application, Beijing Forestry University, Beijing 100083, P. R. China.
authors: Lin
authors: L
authors: Dai
authors: MOE Key Laboratory of Wooden Material Science and Application, Beijing Forestry University, Beijing 100083, P. R. China.
authors: Luying
authors: L
authors: Wang
authors: MOE Key Laboratory of Wooden Material Science and Application, Beijing Forestry University, Beijing 100083, P. R. China.
authors: Lihong
authors: L
authors: Deng
authors: MOE Key Laboratory of Wooden Material Science and Application, Beijing Forestry University, Beijing 100083, P. R. China.
authors: Jing
authors: J
authors: Liu
authors: MOE Key Laboratory of Wooden Material Science and Application, Beijing Forestry University, Beijing 100083, P. R. China.
authors: Jiandu
authors: J
authors: Lei
authors: MOE Key Laboratory of Wooden Material Science and Application, Beijing Forestry University, Beijing 100083, P. R. China.
authors: Dan
authors: D
authors: Li
authors: MOE Key Laboratory of Wooden Material Science and Application, Beijing Forestry University, Beijing 100083, P. R. China.
authors: Jing
authors: J
authors: He
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology*; D037621:Artemisinins / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D045744:Cell Line, Tumor; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D011092:Polyethylene Glycols / Q000737:chemistry*; D012995:Solubility; D013329:Structure-Activity Relationship; D016019:Survival Analysis; D047368:Tumor Burden / Q000187:drug effects; D023041:Xenograft Model Antitumor Assays
chemical_list: D000970:Antineoplastic Agents; D037621:Artemisinins; D011092:Polyethylene Glycols; C039060:artenimol