Synthesis and Properties of Star HPMA Copolymer Nanocarriers Synthesised by RAFT Polymerisation Designed for Selective Anticancer Drug Delivery and Imaging
Synthesis and Properties of Star HPMA Copolymer Nanocarriers Synthesised by RAFT Polymerisation Designed for Selective Anticancer Drug Delivery and Imaging
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DOI：
10.1002/mabi.201400510
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发表时间：
2015-06-01
影响因子：
4.6
通讯作者：
Etrych, Tomas
中科院分区：
文献类型：
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作者：
Chytil, Petr;Koziolova, Eva;Etrych, Tomas
合成了用于实体肿瘤治疗和/或可视化的高分子量星形聚合物药物纳米载体，并测定了它们的物理化学和初步的体外生物学特性。采用可控自由基可逆加成断裂链转移(RAFT)聚合方法，通过N-(2-羟丙基)甲基丙烯酰胺(HPMA)共聚物与聚酰胺胺(PAMAM)树枝状聚合物的接枝反应，制备了水溶性星形聚合物载体。以较高的产率合成了具有较低分散度(约1.2)的M-w值为210(5)~610(5)的星形共聚物。一种模型抗癌药物阿霉素通过联带键与星形聚合物结合，使药物能够在靶肿瘤组织中释放pH控制的药物。星形共聚物载体的活化聚合物臂末端使得能够一点连接靶向配体和/或标记部分。在这项研究中，模型TAMRA荧光染料被用来证明聚合物载体在体外通过光学成像可视化的可行性。星形聚合物载体的定制结构应该有助于合成靶向聚合物-药物结合物，甚至聚合物治疗药物，用于同时传递肿瘤药物和成像。
High-molecular-weight star polymer drug nanocarriers intended for the treatment and/or visualisation of solid tumours were synthesised, and their physico-chemical and preliminary in vitro biological properties were determined. The water-soluble star polymer carriers were prepared by the grafting of poly(amido amine) (PAMAM) dendrimers by hetero-telechelic N-(2-hydroxypropyl)methacrylamide (HPMA) copolymers, synthesised by the controlled radical Reversible Addition Fragmentation chain Transfer (RAFT) polymerisation. The well-defined star copolymers with M-w values ranging from 210(5) to 610(5) showing a low dispersity (approximately 1.2) were prepared in a high yield. A model anticancer drug, doxorubicin, was bound to the star polymer through a hydrazone bond, enabling the pH-controlled drug release in the target tumour tissue. The activated polymer arm ends of the star copolymer carrier enable a one-point attachment for the targeting ligands and/or a labelling moiety. In this study, the model TAMRA fluorescent dye was used to prove the feasibility of the polymer carrier visualisation by optical imaging in vitro. The tailor-made structure of the star polymer carriers should facilitate the synthesis of targeted polymer-drug conjugates, even polymer theranostics, for simultaneous tumour drug delivery and imaging.