Senevirathne Suchithra A, Washington Katherine E, Biewer Michael C, Stefan Mihaela C
Department of Chemistry, University of Texas at Dallas, Richardson, TX, USA.
J Mater Chem B. 2016 Jan 21;4(3):360-370. doi: 10.1039/c5tb02053k. Epub 2015 Dec 16.
Due to the high cost and uncertain success of new drug development, tremendous effort is devoted to increasing the efficacy of established anti-cancer drugs. Development of polymer prodrug conjugates has evolved recently in the nano-medicine field for cancer diagnosis and treatment. The major advantage of using polymer drug conjugates is that the chemical and physical properties of polymers can be tuned to increase the efficacy and to reduce the toxicity of the drug. The stimuli responsiveness provides the release of the prodrug in a controlled manner which avoids undesired side effects, organ damage, and toxicity caused by the fluctuations associated with periodic administration. A large number of anti-cancer drug polymer conjugates have been studied for cancer therapy due to their promising clinical applications in chemotherapy. In this paper, poly(ethylene glycol) (PEG) based anti-cancer drug conjugates will be discussed followed by a review of different types of PEG-b-poly(ε-caprolactone) (PEG-b-PCL) copolymer drug conjugates and histone deacetylase inhibitor polymer conjugates as novel therapeutics. The pH sensitive release of prodrugs will be discussed for polymer prodrug conjugates that are currently under investigation.
由于新药研发成本高昂且成功与否不确定,人们投入了巨大努力来提高现有抗癌药物的疗效。聚合物前药缀合物的研发近年来在癌症诊断与治疗的纳米医学领域不断发展。使用聚合物药物缀合物的主要优势在于,可以调节聚合物的化学和物理性质,以提高药物疗效并降低其毒性。刺激响应性使得前药能够以可控方式释放,从而避免了因定期给药波动导致的不良副作用、器官损伤和毒性。由于其在化疗中具有广阔的临床应用前景,大量抗癌药物聚合物缀合物已被用于癌症治疗研究。本文将讨论基于聚乙二醇(PEG)的抗癌药物缀合物,随后综述不同类型的聚乙二醇-b-聚(ε-己内酯)(PEG-b-PCL)共聚物药物缀合物以及组蛋白去乙酰化酶抑制剂聚合物缀合物作为新型治疗药物的情况。还将讨论目前正在研究的聚合物前药缀合物的前药pH敏感释放。