Polymer-drug conjugates, PDEPT and PELT: basic principles for design and transfer from the laboratory to clinic
Polymer-drug conjugates, PDEPT and PELT: basic principles for design and transfer from the laboratory to clinic
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DOI：
10.1016/s0168-3659(01)00328-5
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发表时间：
2001-07-06
影响因子：
10.8
通讯作者：
Searle, F
中科院分区：
文献类型：
--
作者：
Duncan, R;Gac-Breton, S;Searle, F
目前至少有7种聚合物-药物偶联物作为抗癌药物进入I/II期临床试验。这些包括N-（2-羟丙基）甲基丙烯酰胺（HPMA）共聚物-多柔比星（PK 1，FCE 28068）、HPMA共聚物-紫杉醇（PNU 166945）、HPMA共聚物-喜树碱、PEG-喜树碱、聚谷氨酸-紫杉醇、HPMA共聚物-铂酸盐（AP 5280）以及另外带有半乳糖胺的HPMA共聚物-多柔比星缀合物（PK 2，FCE 28069）。半乳糖胺用作将缀合物靶向肝脏的手段，用于治疗原发性和继发性肝癌。亲溶酶体偶联物的早期临床结果已经引起了人们对该领域的极大兴趣。正在进行的研究是开发（1）含有药物的缀合物，这些药物由于溶解性差或不可控制的毒性而不能进展;（2）针对新靶点的药剂的缀合物;和（3）两步组合，如聚合物导向的酶前药疗法（PDEPT）和聚合物-酶脂质体疗法（PELT）其可导致药物从肿瘤细胞内的聚合物前药或脂质体中爆炸性释放。此外，基于生物响应聚合物的构建体能够促进封闭体逃逸，从而促进大分子药物（肽、蛋白质和寡核苷酸）的胞质内递送也在研究中。(C)2001 Elsevier Science B. V.保留所有权利。
There are now at least seven polymer-drug conjugates that have entered phase I/II clinical trial as anticancer agents. These include N-(2-hydroxypropyl)methacrylamide (HPMA) copolymer-doxorubicin (PK1, FCE28068), HPMA copolymer-paclitaxel (PNU 166945), HPMA copolymer-camptothecin, PEG-camptothecin, polyglutamic acid-paclitaxel an HPMA copolymer-platinate (AP5280) and also an HPMA copolymer-doxorubicin conjugate bearing additionally galactosamine (PK2, FCE28069). The galactosamine is used as a means to target the conjugate to liver for the treatment of primary and secondary liver cancer. Promising early clinical results with lysosomotropic conjugates has stimulated significant interest in this field. Ongoing research is developing (1) conjugates containing drugs that could otherwise not progress due to poor solubility or uncontrollable toxicity; (2) conjugates of agents directed against novel targets; and (3) two-step combinations such as polymer-directed enzyme prodrug therapy (PDEPT) and polymer-enzyme liposome therapy (PELT) that can cause explosive liberation of drug from either polymeric prodrugs or liposomes within the tumour interstitium. Moreover, bioresponsive polymer-based constructs able to promote enclosomal escape and thus intracytoplasmic delivery of macromolecular drugs (peptides, proteins and oligonucleotides) are also under study. (C) 2001 Elsevier Science B.V. All rights reserved.