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

ABSTRACT: 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-?B 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?-1). Conclusively, PEG-TA conjugate displayed superior anti-neoplastic activities and low toxicity, as well as facilitated the delivery of other hydrophobic agents, which appeared to be an innovative strategy for cancer therapy.

SUBMITTER: Zhou Y

PROVIDER: S-EPMC6060375 | biostudies-literature | 2018 Nov

REPOSITORIES: biostudies-literature

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

Zhou Yimeng Y Li Ning N Qiu Zhixia Z Lu Xiaoyu X Fang Min M Chen Xijing X Ren Lili L Wang Guangji G Ouyang Pingkai P

Drug delivery 20181101 1

Triacontanol (TA, C<sub>30</sub>H<sub>62</sub>O), 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 effec ...[more]

PMID: 30022695

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

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

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