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聚合物缀合物作为抗癌纳米药物

Polymer conjugates as anticancer nanomedicines

原文发布日期：2006-08-10

DOI: 10.1038/nrc1958

类型: Review Article

开放获取: 否

要点：

要点翻译：

英文摘要：

摘要翻译：

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文章：

聚合物缀合物作为抗癌纳米药物

Polymer conjugates as anticancer nanomedicines

原文发布日期：2006-08-10

DOI: 10.1038/nrc1958

类型: Review Article

开放获取: 否

要点：

Water-soluble polymers conjugated to proteins and anticancer drugs are in routine clinical use and clinical development as both single agents and components of combination therapy. This is establishing polymer therapeutics as one of the first classes of anticancer nanomedicine. There is growing optimism about the use of ever more sophisticated polymer-based vectors for cancer therapy.
The covalent conjugation of synthetic polymers, particularly poly(ethyleneglycol) (PEG), to protein drugs increases their plasma residence, reduces protein immunogenicity and can increase their therapeutic index. Several PEGylated enzymes (such as L-asparaginase) and cytokines (including interferon-α and granulocyte colony-stimulating factor) have now entered routine clinical use.
Polymer conjugation alters the biodistribution of low-molecular-weight drugs, enabling tumour-specific targeting with reduced access to sites of toxicity. More than ten polymer–anti-tumour conjugates have been transferred into clinical development. They have been designed for lysosomotropic delivery following passive tumour targeting by the enhanced permeability and retention effect (EPR effect) or, in one case, for receptor-mediated targeting by the introduction of a cell-specific ligand. Polyglutamic acid–paclitaxel is showing particular promise in phase III trials in women with non-small-cell lung cancer.
New strategies are making polymer conjugates active against new molecular targets (for example, anti-angiogenics), and the combination of polymer conjugates with low-molecular-weight drugs (which are routinely used in chemotherapy), radiotherapy or tailor-made prodrugs is showing promise. Moreover, the polymer platform provides an ideal opportunity to deliver a drug combination from a single carrier, and combined endocrine therapy and chemotherapy is showing preclincal potential as a breast cancer therapy.
The polymers that have been used clinically so far have a linear polymer architecture. The principles for the design of polymer therapeutics are now being applied to new hyperbranched dendrimers and dendritic polymer architectures. Before clinical evaluation it is essential to establish the safety of new polymers, particularly in respect of general toxicity, immunogenicity and metabolic fate.

要点翻译：

与蛋白质及抗癌药物共轭结合的水溶性聚合物，目前已作为单一药剂或联合疗法的组成部分进入常规临床应用及临床研发阶段。这确立了聚合物治疗剂作为首批抗癌纳米药物之一的地位。人们对使用日益精密化的聚合物载体进行癌症治疗持愈发乐观的态度。
合成聚合物（特别是聚乙二醇PEG）与蛋白质药物的共价结合，可延长其血浆半衰期、降低蛋白质免疫原性，并能提高其治疗指数。数种PEG化酶类（如L-天冬酰胺酶）及细胞因子（包括α-干扰素和粒细胞集落刺激因子）现已进入常规临床应用。
聚合物共轭技术可改变低分子量药物的生物分布特性，实现肿瘤特异性靶向的同时降低其在毒性部位的分布。已有十余种聚合物-抗肿瘤共轭物进入临床研发阶段。这些共轭物被设计为通过增强渗透滞留效应（EPR效应）实现被动肿瘤靶向后进行溶酶体导向递送，或在个别案例中通过引入细胞特异性配体实现受体介导的靶向。聚谷氨酸-紫杉醇共轭物在非小细胞肺癌女性患者的III期临床试验中展现出显著潜力。
新兴策略正推动聚合物共轭物作用于新型分子靶点（如抗血管生成靶点），其与化疗常规低分子药物、放疗或定制前药的联合疗法也展现出前景。此外，聚合物平台为通过单一载体递送复方药物提供了理想途径，联合内分泌疗法与化疗在乳腺癌治疗中显示出临床前潜力。
目前临床应用的聚合物均为线性结构。聚合物治疗剂的设计原理正逐步应用于新型超支化树枝状聚合物及树突状聚合物架构。在进入临床评估前，必须确认新型聚合物的安全性，特别是在全身毒性、免疫原性及代谢归宿方面的表现。

英文摘要：

The transfer of polymer–protein conjugates into routine clinical use, and the clinical development of polymer–anticancer-drug conjugates, both as single agents and as components of combination therapy, is establishing polymer therapeutics as one of the first classes of anticancer nanomedicines. There is growing optimism that ever more sophisticated polymer-based vectors will be a signficant addition to the armoury currently used for cancer therapy.