Enhanced efficacy in drug-resistant cancer cells through synergistic nanoparticle mediated delivery of cisplatin and decitabine.
Enhanced efficacy in drug-resistant cancer cells through synergistic nanoparticle mediated delivery of cisplatin and decitabine.
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DOI：
10.1039/c9na00684b
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发表时间：
2020-03-17
影响因子：
4.7
通讯作者：
中科院分区：
文献类型：
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单药癌症治疗存在几个局限性，包括生物利用度差、清除快和耐药性。联合治疗通过利用不同药物之间的协同作用对抗癌细胞来解决这些问题。特别是，表观遗传疗法与常规化疗剂的组合可以改善初始肿瘤反应并克服获得性耐药性。将多种治疗剂共包封到单个聚合物纳米颗粒中是用于增强治疗效果和改善药代动力学特征的许多方法之一。在这项研究中，不同类型的聚（乳酸-共-乙醇酸）（PLGA）纳米粒子（NP），矩阵和核壳（CS），同时封装的去甲基化药物，地西他滨，和一个有效的抗癌剂，顺铂进行了研究。结果表明，通过改变CS结构的配置，可以调整释放曲线。为了研究与顺铂相比这是否可以增强抗癌效果，将人卵巢癌细胞系（A2780）及其顺铂抗性变体（A2780 cis）暴露于游离顺铂和CS-NP。使用CS-NP在两种细胞系中（A2780和A2780 cis的存活率分别为11%和51%）获得了比顺铂单独使用（A2780和A2780 cis的存活率分别为27%和82%）或与地西他滨联合使用（A2780和A2780 cis的存活率分别为22%和96%）更好的反应。顺铂和地西他滨在通过电流体动力学处理产生的纳米颗粒中的共包封。在单一纳米载体中组合多种治疗剂可能有助于克服癌症治疗中单一疗法的缺点。
There are several limitations with monodrug cancer therapy, including poor bioavailability, rapid clearance and drug resistance. Combination therapy addresses these by exploiting synergism between different drugs against cancer cells. In particular, the combination of epigenetic therapies with conventional chemotherapeutic agents can improve the initial tumour response and overcome acquired drug resistance. Co-encapsulation of multiple therapeutic agents into a single polymeric nanoparticle is one of the many approaches taken to enhance therapeutic effect and improve the pharmacokinetic profile. In this study, different types of poly(lactic-co-glycolic acid) (PLGA) nanoparticles (NPs), matrix and core–shell (CS), were investigated for simultaneous encapsulation of a demethylating drug, decitabine, and a potent anticancer agent, cisplatin. It was shown that by altering the configuration of the CS structure, the release profile could be tuned. In order to investigate whether this could enhance the anticancer effect compared to cisplatin, human ovarian carcinoma cell line (A2780) and its cisplatin resistant variant (A2780cis) were exposed to free cisplatin and the CS–NPs. A better response was obtained in both cell lines (11% and 51% viability of A2780 and A2780cis, respectively) using CS–NPs than cisplatin alone (27%, 82% viability of A2780 and A2780cis, respectively) or in combination with decitabine (22%, 96% viability of A2780 and A2780cis, respectively) at equivalent doses (10 μM). Co-encapsulation of cisplatin and decitabine in nanoparticles produced by electrohydrodynamic processing. Combination of multiple therapeutic agents in a single nano-carrier could potentially help to overcome drawbacks of monotherapy in cancer treatment.
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影响因子：
--
作者：
Bayat Mokhtari R;Homayouni TS;Baluch N;Morgatskaya E;Kumar S;Das B;Yeger H
通讯作者：
Yeger H
影响因子：
8
作者：
Reardon PJ;Parhizkar M;Harker AH;Browning RJ;Vassileva V;Stride E;Pedley RB;Edirisinghe M;Knowles JC
通讯作者：
Knowles JC
影响因子：
5.5
作者：
Sorensen, Belinda Halling;Thorsteinsdottir, Unnur Arna;Lambert, Ian Henry
通讯作者：
Lambert, Ian Henry
小分子前药和纳米药物递送的组合：用于癌症治疗的两亲性药物-药物缀合物
影响因子：
15
作者：
Huang, Ping;Wang, Dali;Yan, Deyue
通讯作者：
Yan, Deyue
影响因子：
8
作者：
Briot T;Roger E;Lautram N;Verger A;Clavreul A;Lagarce F
通讯作者：
Lagarce F