Electroneutral polymersomes for combined cancer chemotherapy
Electroneutral polymersomes for combined cancer chemotherapy
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DOI：
10.1016/j.actbio.2018.09.005
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发表时间：
2018-10-15
影响因子：
9.7
通讯作者：
Callan, Bridgeen
中科院分区：
文献类型：
--
作者：
Aibani, Noorjahan;Nesbitt, Heather;Callan, Bridgeen
联合化疗提供了一种重要的治疗手段，作为一种辅助和新辅助治疗，这种从单一疗法到联合疗法的重点转移导致了人们对药物递送系统(DDS)的兴趣增加。DDSS，如多聚体，能够同时包裹大量具有亲水性和疏水性的多种药物，并提供一种机制来对抗多药耐药癌症和患者对所使用的细胞毒性化合物的耐受性差。本文报道了一种对多种药物(阿霉素、5-氟尿嘧啶和亚叶酸钙)具有高包封率的新型电子中和聚合物的配方和评价。建立了聚合体在体内的生物分布，发现它们在肿瘤组织中大量积累。在体外(BxPC-3细胞株)和体内(瘤内和静脉给药后)对包裹三种化疗药物的聚合体进行了评估，并与相同浓度的三种药物溶液进行了比较。我们报告说，在所有实验中，我们的联合载药多聚体具有更好的疗效和更高的最大耐受量。此外，瘤内注射复合药物载药多聚体13天后，与自由组合溶液相比，肿瘤体积减少了62%。然而，当静脉给药时，观察到的差异较小，为13%，重要的是，多聚体DDS表现出的心脏毒性较小。在这项研究中，比较了一些与生存相关的基因在自由化疗联合治疗的肿瘤中的表达，以及这些基因在含有这些药物的聚合体治疗的肿瘤中的表达，并讨论了结果的意义。(C)2018 Acta Materialia Inc.由Elsevier Ltd.出版。保留所有权利。
Combination cancer chemotherapy provides an important treatment tool, both as an adjuvant and neoadjuvant treatment, this shift in focus from mono to combination therapies has led to increased interest in drug delivery systems (DDS). DDSs, such as polymersomes, are capable of encapsulating large amounts of multiple drugs with both hydrophilic and hydrophobic properties simultaneously, as well as offering a mechanism to combat multi drug resistant cancers and poor patient tolerance of the cytotoxic compounds utilised. In this article, we report the formulation and evaluation of a novel electroneutral polymersome capable of high encapsulation efficacies for multiple drugs (Doxorubicin, 5-Fluorouracil and leucovorin). The in-vivo biodistribution of the polymersome were established and they were found to accumulate largely in tumour tissue. Polymersome encapsulating the three chemotherapeutic drugs were assessed both in-vitro (BxPC-3 cell line) and in-vivo (following intratumoral and intravenous administration) and compared with the same concentration of the three drugs in solution. We report better efficacy and higher maximum tolerated dose for our combination drug loaded polymersomes in all experiments. Furthermore, intratumorally injected combination drug loaded polymersomes exhibited a 62% reduction in tumour volume after 13 days when compared with the free combination solutions. A smaller differential of 13% was observed for when treatment was administered intravenously however, importantly less cardiotoxicity was displayed from the polymersomal DDS. In this study, expression of a number of survival-relevant genes in tumours treated with the free chemotherapy combination was compared with expression of those genes in tumours treated with the polymersomes harbouring those drugs and the significance of findings is discussed. (C) 2018 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.