Tumor Specific and Renal Excretable Star-like Triblock Polymer–Doxorubicin Conjugates for Safe and Efficient Anticancer Therapy,Biomacromolecules

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Tumor Specific and Renal Excretable Star-like Triblock Polymer–Doxorubicin Conjugates for Safe and Efficient Anticancer Therapy
Biomacromolecules ( IF 5.5 ) Pub Date : 2018-05-09 00:00:00 , DOI: 10.1021/acs.biomac.8b00425
Hao Tang , Jiajing Zhang ₁ , Jin Tang , Yi Shen , Wenxuan Guo , Min Zhou , Ruihua Wang , Ni Jiang , Zhihua Gan , Qingsong Yu

Affiliation

Efficient tumor accumulation and body clearance are two paralleled requirements for ideal nanomedicines. However, it is hard for both to be met simultaneously. The inefficient clearance often restrains the application of drug delivery systems (DDSs), especially for high-dosage administration. In this study, the star-like and block structures are combined to enhance the tumor specific targeting of the parent structures and obtain additional renal excretion property. The influences of polymer architectures and chemical compositions on the physicochemical and biological properties, particularly the simultaneous achievement of tumor accumulation and renal clearance, have been investigated. Among the tested conjugates, an eight-arm triblock star polymer based on poly(ethylene glycol) (PEG) and poly(N-(2-hydroxyl) methacrylamide) (PHPMA) is found to simultaneously fulfill the requirements of superior tumor accumulation and efficient renal clearance due to the appropriate micelle size and reversible aggregation process. On the basis of this conjugate, 60 mg/kg of Dox equivalent (much higher than the maximum tolerated dose (MTD) of Dox) can be administered to efficiently suppress tumor growth without causing any obvious toxicity. This work provides a new approach to design polymer–drug conjugates for tumor specific application, which can simultaneously address the efficacy and safety concerns.

中文翻译：

肿瘤特异性和肾脏可排泄的星形三嵌段聚合物-阿霉素结合可安全有效地进行抗癌治疗

有效的肿瘤蓄积和体内清除率是理想纳米药物的两个平行要求。但是，很难同时满足这两个条件。清除效率低下通常会限制药物输送系统（DDS）的应用，尤其是对于高剂量给药。在这项研究中，将星形和块状结构结合起来以增强对母体结构的肿瘤特异性靶向，并获得额外的肾脏排泄特性。研究了聚合物结构和化学组成对理化和生物学特性的影响，尤其是同时实现肿瘤蓄积和肾脏清除的影响。在测试的缀合物中，一种基于聚乙二醇（PEG）和聚N的八臂三嵌段星形聚合物由于适当的胶束大小和可逆的聚集过程，发现-（2-羟基）甲基丙烯酰胺）（PHPMA）可同时满足优异的肿瘤蓄积和有效的肾脏清除的要求。在这种缀合物的基础上，可以服用60 mg / kg的Dox当量（远高于Dox的最大耐受剂量（MTD））以有效抑制肿瘤的生长而不会引起任何明显的毒性。这项工作提供了一种新方法来设计用于肿瘤特异性应用的聚合物-药物偶联物，可以同时解决功效和安全性问题。

更新日期：2018-05-09

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