title: Annonaceous acetogenins nanosuspensions stabilized by PCL-PEG block polymer: significantly improved antitumor efficacy.
abstract: Annonaceous acetogenins (ACGs) have shown superior antitumor activity against a variety of cancer cell lines, but their clinical application has been limited by their poor solubility. In this study, ACGs-nanosuspensions (NSps) were successfully prepared by a precipitation ultrasonic method using monomethoxypoly (ethylene glycol)2000-poly (ε-caprolactone)2000 (mPEG2000-PCL2000) as a stabilizer. The resultant ACGs-NSps had a mean particle size of 123.2 nm, a zeta potential of -20.17 mV, and a high drug payload of 73.68%. ACGs-NSps were quite stable in various physiological solutions, and they exhibited sustained drug release. Compared to free drug, ACGs-NSps exhibited stronger cytotoxicity against 4T1, MCF-7, and HeLa cells. An in vivo real-time biodistribution investigation after labeling with 1,1'-dioctadecyltetramethyl indotricarbocyanine iodide, a noninvasive near-infrared fluorescence probe, demonstrated that ACGs-NSps could effectively accumulate in tumor. An in vivo antitumor activity study in 4T1 tumor-bearing mice revealed that ACGs-NSps achieved much better therapeutic efficacy than the traditional dosage form (oil solution) even at 1/10 of the dose (74.83% vs 45.53%, P<0.05), demonstrating that NSp was a good dosage form for ACGs to treat cancer.
authors.affiliation: Key Laboratory of Bioactive Substances and Resources Utilization of Chinese Herbal Medicine, Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing.
authors.forename: Jingyi
authors.initials: J
authors.lastname: Hong
authors.affiliation: Key Laboratory of Bioactive Substances and Resources Utilization of Chinese Herbal Medicine, Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing; School of Pharmacy, Heilongjiang University of Chinese Medicine, Harbin, People's Republic of China.
authors.forename: Yanhong
authors.initials: Y
authors.lastname: Li
authors.affiliation: Key Laboratory of Bioactive Substances and Resources Utilization of Chinese Herbal Medicine, Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing.
authors.forename: Yijing
authors.initials: Y
authors.lastname: Li
authors.affiliation: Key Laboratory of Bioactive Substances and Resources Utilization of Chinese Herbal Medicine, Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing; School of Pharmacy, Heilongjiang University of Chinese Medicine, Harbin, People's Republic of China.
authors.forename: Yao
authors.initials: Y
authors.lastname: Xiao
authors.affiliation: School of Pharmacy, Heilongjiang University of Chinese Medicine, Harbin, People's Republic of China.
authors.forename: Haixue
authors.initials: H
authors.lastname: Kuang
authors.affiliation: Key Laboratory of Bioactive Substances and Resources Utilization of Chinese Herbal Medicine, Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing.
authors.forename: Xiangtao
authors.initials: X
authors.lastname: Wang
mesh_terms: D054378:Acetogenins / Q000494:pharmacology; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D016923:Cell Death / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D065546:Drug Liberation; D005260:Female; D006367:HeLa Cells; D006801:Humans; D020128:Inhibitory Concentration 50; D061986:MCF-7 Cells; D008807:Mice, Inbred BALB C; D053758:Nanoparticles / Q000737:chemistry*; D010316:Particle Size; D011091:Polyesters / Q000737:chemistry*; D011092:Polyethylene Glycols / Q000737:chemistry*; D013535:Suspensions; D014018:Tissue Distribution / Q000187:drug effects; D016896:Treatment Outcome
chemical_list: D054378:Acetogenins; D000970:Antineoplastic Agents; D011091:Polyesters; D013535:Suspensions; C016240:polycaprolactone; D011092:Polyethylene Glycols
keywords: annonaceous acetogenins; antitumor efficacy; biodistribution; mPEG2000–PCL2000; near–infrared fluorescence