Folate-modified Annonaceous acetogenins nanosuspensions and their improved antitumor efficacy

• Published in: International journal of nanomedicine 2017-01, Vol.12, p.5053-5067
• Main Authors: Hong, Jingyi, Sun, Zhonghao, Li, Yijing, Guo, Yifei, Liao, Yonghong, Liu, Meifeng, Wang, Xiangtao
• Format: Article
• Language: English
• Subjects: Acetogenins - chemistry; Acetogenins - pharmacokinetics; Acetogenins - pharmacology; Animals; Annonaceae - chemistry; Annonaceous acetogenins; Anti-tumor activity; Antineoplastic Agents, Phytogenic - chemistry; Antineoplastic Agents, Phytogenic - pharmacokinetics; Antineoplastic Agents, Phytogenic - pharmacology; beta-Cyclodextrins - chemistry; Body Weight - drug effects; Breast cancer; Cell Line, Tumor; Cytotoxicity; Drug delivery systems; Drug Delivery Systems - methods; Experiments; Female; Folate; Folic acid; Folic Acid - chemistry; Folic Acid - pharmacology; Herbal medicine; Humans; Laboratory animals; Lecithins - chemistry; Mice, Inbred BALB C; Nanoparticles; Nanostructures - chemistry; Nanosuspensions; Natural products; Original Research; Particle Size; Physiological aspects; Properties; Solubility; Studies; Suspensions - chemistry; Suspensions - pharmacology; Targeted drug delivery; Tissue Distribution; Tumors; Vitamin B; Xenograft Model Antitumor Assays
• ISSN: 1178-2013; 1176-9114; 1178-2013
• DOI: 10.2147/IJN.S134284

Annonaceous acetogenins (ACGs) are a large family of fatty acid derived natural products that are exclusively isolated from the species. Many members of this diverse family have a broad spectrum of biological activities, the most impressive of which is anticancer activity. However, their poor solubility and severe toxicity restrict their clinical application, and their complicated composition hinders their formulation and drug delivery. In this study, β-cyclodextrin was modified with folic acid (FA) and then combined with soybean lecithin to prepare FA-modified ACGs nanosuspensions (FA-ACGs-NSps). The obtained FA-ACGs-NSps had a high drug payload of 57.59% and average particle size of 199.5 nm, and they exhibited sustained drug release within 142 hours. In comparison with ACGs-NSps, FA-ACGs-NSps showed significantly enhanced cytotoxicity and higher cell uptake toward folate receptor-positive 4T1 cell lines. An in vivo study demonstrated that FA-ACGs-NSps more effectively accumulated in tumors and enhanced the antitumor therapeutic efficacy with less toxicity in 4T1 tumor bearing mice. Therefore, FA-ACGs-NSps may be a promising drug delivery system for ACGs to improve their therapeutic window and may be suitable for clinical application to treat folate-positive tumors.