Oltra Núria Sancho, Nair Praful, Discher Dennis E
Biophysical Engineering Laboratory, Department of Chemical & Biomolecular Engineering, University of Pennsylvania, Philadelphia, Pennsylvania 19104; email:
Annu Rev Chem Biomol Eng. 2014;5:281-99. doi: 10.1146/annurev-chembioeng-060713-040447.
Polymersome vesicles and wormlike filomicelles self-assembled with amphiphilic, degradable block copolymers have recently shown promise in application to cancer therapy. In the case of filomicelles, dense, hydrophilic brushes of poly(ethylene glycol) on these nanoparticles combine with flexibility to nonspecifically delay clearance by phagocytes in vivo, which has motivated the development of "self" peptides that inhibit nanoparticle clearance through specific interactions. Delayed clearance, as well as robustness of polymer assemblies, opens the dosage window for delivery of increased drug loads in the polymer assemblies and increased tumor accumulation of drug(s). Antibody-targeting and combination therapies, such as with radiotherapy, are emerging in preclinical animal models of cancer. Such efforts are expected to combine with further advances in polymer composition, structure, and protein/peptide functionalization to further enhance transport through the circulation and permeation into disease sites.
最近,由两亲性、可降解嵌段共聚物自组装而成的聚合物囊泡和蠕虫状丝状胶束在癌症治疗应用中显示出了前景。就丝状胶束而言,这些纳米颗粒上密集的聚乙二醇亲水刷与柔韧性相结合,可在体内非特异性地延迟吞噬细胞的清除,这推动了通过特异性相互作用抑制纳米颗粒清除的“自”肽的开发。清除延迟以及聚合物组装体的稳定性,为在聚合物组装体中递送增加的药物负载量以及增加药物在肿瘤中的积累打开了剂量窗口。在癌症临床前动物模型中,抗体靶向和联合疗法(如与放射疗法联合)正在兴起。预计这些努力将与聚合物组成、结构以及蛋白质/肽功能化方面的进一步进展相结合,以进一步增强通过循环的运输以及向疾病部位的渗透。