Nanotechnology Characterization Laboratory, Cancer Research Technology Program, Leidos Biomedical Research, Inc., Frederick National Laboratory for Cancer Research, Frederick, Maryland, 21702, USA.
AAPS J. 2017 Nov;19(6):1632-1642. doi: 10.1208/s12248-017-0152-y. Epub 2017 Oct 10.
Genomic analyses from patients with cancer have improved the understanding of the genetic elements that drive the disease, provided new targets for treating this relentless disease, and offered criteria for stratifying patient populations that will benefit most from treatments. In the last decade, several new targeted therapies have been approved by the FDA based on these omics findings, leading to significantly improved survival and quality of life for select patient populations. However, many of these precision medicines, e.g., nucleic acid-based therapies and antibodies, suffer from poor plasma stability, suboptimal pharmacokinetic properties, and immunological toxicities that prohibit their clinical translation. Nanotechnology is being explored as a delivery platform that can enable the successful delivery of these precision medicine treatments without these limitations. These precision nanomedicines are able to protect the cargo from degradation or premature/burst release prior to accumulation at the tumor site and improve the selectivity to cancer cells by incorporating ligands that can target receptors overexpressed on the cancer cell surface. Here, we review the development of several precision nanomedicines based on genomic analysis of clinical samples, actively targeted nanoparticle delivery systems in the clinic, and the pathophysiological barriers of the tumor microenvironment. Successful translation of these precision nanomedicine initiatives will require an effective collaboration between basic and clinical investigators to match the right patient with the right therapies and to deliver them at therapeutic concentrations which will improve overall treatment responses.
从癌症患者身上进行的基因组分析提高了人们对驱动疾病的遗传因素的认识,为治疗这种无情的疾病提供了新的靶点,并为最能从治疗中受益的患者人群分层提供了标准。在过去的十年中,FDA 根据这些组学发现批准了几种新的靶向疗法,为特定患者群体带来了显著提高的生存率和生活质量。然而,许多这些精准药物,例如基于核酸的疗法和抗体,存在血浆稳定性差、药代动力学性能不佳和免疫毒性等问题,限制了它们的临床转化。纳米技术正被探索作为一种可以成功递送这些精准药物治疗而没有这些限制的平台。这些精准纳米药物能够保护货物免受降解或过早/爆发性释放,直到在肿瘤部位积累,并通过整合可以靶向癌细胞表面过度表达的受体的配体来提高对癌细胞的选择性。在这里,我们回顾了基于临床样本的基因组分析、临床中主动靶向的纳米颗粒递药系统以及肿瘤微环境的病理生理障碍等方面的几种精准纳米药物的开发。这些精准纳米药物的成功转化将需要基础和临床研究人员之间的有效合作,以将合适的患者与合适的治疗方法相匹配,并以治疗浓度递送给他们,从而提高整体治疗反应。