Superior anti-neoplastic activities of triacontanol-PEG conjugate: synthesis, characterization and biological evaluations

Autor: Yimeng Zhou, Ning Li, Zhixia Qiu, Xiaoyu Lu, Min Fang, Xijing Chen, Lili Ren, Guangji Wang, Pingkai Ouyang
Jazyk: angličtina
Rok vydání: 2018
Předmět:
Zdroj: Drug Delivery, Vol 25, Iss 1, Pp 1546-1559 (2018)
Druh dokumentu: article
ISSN: 1071-7544
1521-0464
10717544
DOI: 10.1080/10717544.2018.1477864
Popis: Triacontanol (TA, C30H62O), abundantly present in plant cuticle waxes and bee waxes, has been found to display promising anti-neoplastic potentials. As a long chain fatty alcohol, TA possesses limited aqueous solubility, which hinders its medicinal application. To overcome its solubility barrier, a polymer prodrug was synthesized through attaching TA to poly ethylene glycol (PEG), using succinic acid as a linker with bifunctional amide and ester bonds. Anti-neoplastic effects of PEG-TA were assessed in LoVo and MCF7 cells, anti-proliferative and apoptosis-inducing activities were subsequently confirmed in mouse xenograft model. Encouragingly, PEG-TA possessed selective anti-cancer ability. It did not exhibit significant cytotoxicity on normal cells. Mechanistic examination revealed inhibition of NF-κB nuclear translocation, suppression on matrix degradation enzyme and down-regulation of angiogenic signaling might contribute to its anti-malignant effects. Pharmacokinetics clearly indicated PEGylated TA (named as mPEG2K-SA-TA) substantially enhanced TA delivery with increased plasma exposure (19,791 vs. 336.25 ng·mL−1·h−1, p
Databáze: Directory of Open Access Journals
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