University of Oxford, Department of Clinical Pharmacology, Old Road Campus Research Building, Old Road Campus, off Roosevelt Drive, Headington, Oxford OX3 7DQ United Kingdom.
Adv Drug Deliv Rev. 2010 Feb 17;62(2):240-5. doi: 10.1016/j.addr.2009.12.003. Epub 2009 Dec 29.
Hydrophilic polymers are widely used already for steric stabilisation of bioactive proteins, changing their pharmacokinetics and modifying their interactions with the biological environment. Polymers may also be conjugated to biological surfaces, such as viruses, bacteria and mammalian cells, also to endow steric protection and changed properties. Reactive polymers based on N-[2-hydroxypropyl]methacrylamide have shown particular promise for surface coating of viruses, particularly adenovirus, and here we describe the important observations and innovations arising from this combination of chemical and genetic engineering. Adenovirus is a versatile agent that already finds important experimental applications as a recombinant vaccine, and also for cancer therapy, although its activity in both settings is often limited by a potent antibody-neutralising response in humans that is generally not seen in experimental animals. Coating with HPMA copolymers provides protection against neutralisation by antibodies and complement, and covalent linkage of novel ligands to the surface of the polymer can endow new infectious tropisms, mediated through different receptors, that can expand the potential applications of this versatile technology for a range of settings.
亲水性聚合物已广泛用于生物活性蛋白质的空间稳定化，改变其药代动力学并修饰其与生物环境的相互作用。聚合物也可以与生物表面（如病毒、细菌和哺乳动物细胞）结合，从而提供空间保护和改变性质。基于 N-[2-羟丙基]甲基丙烯酰胺的反应性聚合物在病毒，特别是腺病毒的表面涂层方面显示出特殊的前景，在这里我们描述了这种化学和遗传工程组合带来的重要观察结果和创新。腺病毒是一种多功能制剂，已经作为重组疫苗在实验中找到了重要的应用，也用于癌症治疗，尽管其在这两种情况下的活性通常都受到人类中强大的抗体中和反应的限制，而在实验动物中通常不会出现这种反应。用 HPMA 共聚物进行涂层可防止抗体和补体的中和，并且通过不同的受体，将新型配体共价连接到聚合物表面可以赋予新的感染嗜性，从而可以扩展这种多功能技术在一系列环境中的潜在应用。
