Superior anti-neoplastic activities of triacontanol-PEG conjugate: synthesis, characterization and biological evaluations
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...
| Main Authors: | , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Taylor & Francis Group
2018-01-01
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| Series: | Drug Delivery |
| Subjects: | |
| Online Access: | http://dx.doi.org/10.1080/10717544.2018.1477864 |
| _version_ | 1831774242681651200 |
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| author | Yimeng Zhou Ning Li Zhixia Qiu Xiaoyu Lu Min Fang Xijing Chen Lili Ren Guangji Wang Pingkai Ouyang |
| author_facet | Yimeng Zhou Ning Li Zhixia Qiu Xiaoyu Lu Min Fang Xijing Chen Lili Ren Guangji Wang Pingkai Ouyang |
| author_sort | Yimeng Zhou |
| collection | DOAJ |
| description | 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 < .001), mean residence time (8.46 vs. 2.95 h, p < .001) and elimination half-life (7.78 vs. 2.57 h, p < .001) compared to those of original TA. Moreover, mPEG2K-SA-TA appeared to be safe in preliminary toxicological assessment. PEGylated TA also emerged as a functional carrier to deliver hydrophobic chemotherapeutic agents, since it readily self-assembled to micelles in aqueous solution with a low critical micelle concentration (CMC, 19.1 µg·mL−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. |
| first_indexed | 2024-12-22T08:50:43Z |
| format | Article |
| id | doaj.art-d0cb1642dc6d4db0b8cdccd6117ef9d0 |
| institution | Directory Open Access Journal |
| issn | 1071-7544 1521-0464 |
| language | English |
| last_indexed | 2024-12-22T08:50:43Z |
| publishDate | 2018-01-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | Drug Delivery |
| spelling | doaj.art-d0cb1642dc6d4db0b8cdccd6117ef9d02022-12-21T18:31:58ZengTaylor & Francis GroupDrug Delivery1071-75441521-04642018-01-012511546155910.1080/10717544.2018.14778641477864Superior anti-neoplastic activities of triacontanol-PEG conjugate: synthesis, characterization and biological evaluationsYimeng Zhou0Ning Li1Zhixia Qiu2Xiaoyu Lu3Min Fang4Xijing Chen5Lili Ren6Guangji Wang7Pingkai Ouyang8China Pharmaceutical UniversityChina Pharmaceutical UniversityChina Pharmaceutical UniversityChina Pharmaceutical UniversityChina Pharmaceutical UniversityChina Pharmaceutical UniversityNanjing Tech UniversityChina Pharmaceutical UniversityNanjing Tech UniversityTriacontanol (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 < .001), mean residence time (8.46 vs. 2.95 h, p < .001) and elimination half-life (7.78 vs. 2.57 h, p < .001) compared to those of original TA. Moreover, mPEG2K-SA-TA appeared to be safe in preliminary toxicological assessment. PEGylated TA also emerged as a functional carrier to deliver hydrophobic chemotherapeutic agents, since it readily self-assembled to micelles in aqueous solution with a low critical micelle concentration (CMC, 19.1 µg·mL−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.http://dx.doi.org/10.1080/10717544.2018.1477864pegylated triacontanoltriacontanolmicelledrug deliveryanti-neoplastic |
| spellingShingle | Yimeng Zhou Ning Li Zhixia Qiu Xiaoyu Lu Min Fang Xijing Chen Lili Ren Guangji Wang Pingkai Ouyang Superior anti-neoplastic activities of triacontanol-PEG conjugate: synthesis, characterization and biological evaluations Drug Delivery pegylated triacontanol triacontanol micelle drug delivery anti-neoplastic |
| title | Superior anti-neoplastic activities of triacontanol-PEG conjugate: synthesis, characterization and biological evaluations |
| title_full | Superior anti-neoplastic activities of triacontanol-PEG conjugate: synthesis, characterization and biological evaluations |
| title_fullStr | Superior anti-neoplastic activities of triacontanol-PEG conjugate: synthesis, characterization and biological evaluations |
| title_full_unstemmed | Superior anti-neoplastic activities of triacontanol-PEG conjugate: synthesis, characterization and biological evaluations |
| title_short | Superior anti-neoplastic activities of triacontanol-PEG conjugate: synthesis, characterization and biological evaluations |
| title_sort | superior anti neoplastic activities of triacontanol peg conjugate synthesis characterization and biological evaluations |
| topic | pegylated triacontanol triacontanol micelle drug delivery anti-neoplastic |
| url | http://dx.doi.org/10.1080/10717544.2018.1477864 |
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