Histone Deacetylase Inhibitor (HDACi) Conjugated Polycaprolactone for Combination Cancer Therapy.
Histone Deacetylase Inhibitor (HDACi) Conjugated Polycaprolactone for Combination Cancer Therapy.
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DOI：
10.1021/acs.biomac.8b00221
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发表时间：
2018-03-12
影响因子：
6.2
通讯作者：
Stefan MC
中科院分区：
文献类型：
--
作者：
Kularatne RN;Washington KE;Bulumulla C;Calubaquib EL;Biewer MC;Oupicky D;Stefan MC
短链脂肪酸，4-苯基丁酸（PBA），用于治疗尿素循环障碍和镰状细胞病作为内质网应激抑制剂。PBA也被称为组蛋白脱乙酰酶抑制剂（HDACi）。我们在这里报告的效果，联合治疗HeLa癌细胞使用PBA作为HDACi与抗癌药物，阿霉素（DOX）。合成了γ-4-苯基丁酸酯-ε-己内酯单体，并在NdCl 3·3 TEP/TIBA（TEP =磷酸三乙酯，TIBA =三异丁基铝）催化体系中聚合得到聚（γ-4-苯基丁酸酯-ε-己内酯）（PPBCL）均聚物。DOX负载的纳米颗粒由PPBCL均聚物使用聚（乙二醇）作为表面活性剂制备。这些纳米颗粒的包封率高达88%。负载DOX的纳米颗粒显示在pH 5和37 °C下在12小时内累积释放>95%的DOX，并且通过1H NMR光谱监测PBA释放。在对HeLa细胞进行的细胞毒性研究中可以明显地看到组合疗法的效率，其中在用负载DOX的纳米颗粒处理后仅观察到约20%的细胞活力。对HeLa细胞的这种剧烈的细胞毒性作用是DOX和PBA分别对DNA链和HDAC酶的双重作用的结果。总体而言，该研究显示了与单独使用抗癌药物治疗相比，HDACi和DOX抗癌药物联合治疗的潜力。
The short chain fatty acid, 4-phenylbutyric acid (PBA), is used for the treatment of urea cycle disorders and sickle cell disease as an endoplasmic reticulum stress inhibitor. PBA is also known as a histone deacetylase inhibitor (HDACi). We report here the effect of combination therapy on HeLa cancer cells using PBA as the HDACi together with the anticancer drug, doxorubicin (DOX). We synthesized γ-4-phenylbutyrate–ε-caprolactone monomer which was polymerized to form poly(γ-4-phenylbutyrate–ε-caprolactone) (PPBCL) homopolymer using NdCl3·3TEP/TIBA (TEP = triethyl phosphate, TIBA = triisobutylaluminum) catalytic system. DOX-loaded nanoparticles were prepared from the PPBCL homopolymer using poly(ethylene glycol) as a surfactant. An encapsulation efficiency as high as 88% was obtained for these nanoparticles. The DOX-loaded nanoparticles showed a cumulative release of >95% of DOX at pH 5 and 37 °C within 12 h, and PBA release was monitored by 1H NMR spectroscopy. The efficiency of the combination therapy can notably be seen in the cytotoxicity study carried out on HeLa cells, where only ~20% of cell viability was observed after treatment with the DOX-loaded nanoparticles. This drastic cytotoxic effect on HeLa cells is the result of the dual action of DOX and PBA on the DNA strands and the HDAC enzymes, respectively. Overall, this study shows the potential of combination treatment with HDACi and DOX anticancer drug as compared to the treatment with an anticancer drug alone.
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影响因子：
4.9
作者：
Robey RW;Chakraborty AR;Basseville A;Luchenko V;Bahr J;Zhan Z;Bates SE
通讯作者：
Bates SE
影响因子：
2.6
作者：
Thorn CF;Oshiro C;Marsh S;Hernandez-Boussard T;McLeod H;Klein TE;Altman RB
通讯作者：
Altman RB
影响因子：
6.5
作者：
Basseri, Sana;Lhotak, Sarka;Austin, Richard C.
通讯作者：
Austin, Richard C.
影响因子：
4.6
作者：
Alfurhood JA;Sun H;Kabb CP;Tucker BS;Matthews JH;Luesch H;Sumerlin BS
通讯作者：
Sumerlin BS
DOI：
10.1039/c6tb03038f
发表时间：
2017-03-21
期刊：
Journal of materials chemistry. B
影响因子：
--
作者：
Senevirathne SA;Washington KE;Miller JB;Biewer MC;Oupicky D;Siegwart DJ;Stefan MC
通讯作者：
Stefan MC