Kydd Janel, Jadia Rahul, Velpurisiva Praveena, Gad Aniket, Paliwal Shailee, Rai Prakash
Department of Biomedical Engineering and Biotechnology, University of Massachusetts, 1 University Ave, Lowell, MA 01854, USA.
Confocal Imaging Core, Beth Israel Deaconess Medical Center, 330 Brookline Avenue Boston, MA 02215, USA.
Pharmaceutics. 2017 Oct 14;9(4):46. doi: 10.3390/pharmaceutics9040046.
Cancer cells have characteristics of acquired and intrinsic resistances to chemotherapy treatment-due to the hostile tumor microenvironment-that create a significant challenge for effective therapeutic regimens. Multidrug resistance, collateral toxicity to normal cells, and detrimental systemic side effects present significant obstacles, necessitating alternative and safer treatment strategies. Traditional administration of chemotherapeutics has demonstrated minimal success due to the non-specificity of action, uptake and rapid clearance by the immune system, and subsequent metabolic alteration and poor tumor penetration. Nanomedicine can provide a more effective approach to targeting cancer by focusing on the vascular, tissue, and cellular characteristics that are unique to solid tumors. Targeted methods of treatment using nanoparticles can decrease the likelihood of resistant clonal populations of cancerous cells. Dual encapsulation of chemotherapeutic drug allows simultaneous targeting of more than one characteristic of the tumor. Several first-generation, non-targeted nanomedicines have received clinical approval starting with Doxil in 1995. However, more than two decades later, second-generation or targeted nanomedicines have yet to be approved for treatment despite promising results in pre-clinical studies. This review highlights recent studies using targeted nanoparticles for cancer treatment focusing on approaches that target either the tumor vasculature (referred to as 'vascular targeting'), the tumor microenvironment ('tissue targeting') or the individual cancer cells ('cellular targeting'). Recent studies combining these different targeting methods are also discussed in this review. Finally, this review summarizes some of the reasons for the lack of clinical success in the field of targeted nanomedicines.
癌细胞具有对化疗产生获得性和内在抗性的特征，这归因于恶劣的肿瘤微环境，给有效的治疗方案带来了重大挑战。多药耐药性、对正常细胞的附带毒性以及有害的全身副作用构成了重大障碍，因此需要替代的、更安全的治疗策略。传统的化疗给药方式成效甚微，原因在于其作用的非特异性、被免疫系统摄取和快速清除、随后的代谢改变以及肿瘤穿透性差。纳米医学可以通过聚焦实体瘤特有的血管、组织和细胞特征，提供一种更有效的癌症靶向治疗方法。使用纳米颗粒的靶向治疗方法可以降低癌细胞产生耐药克隆群体的可能性。化疗药物的双重封装能够同时靶向肿瘤的多个特征。自1995年多柔比星脂质体（Doxil）获批以来，几种第一代非靶向纳米药物已获得临床批准。然而，二十多年后的今天，尽管第二代或靶向纳米药物在临床前研究中取得了令人鼓舞的结果，但仍未获批用于治疗。本综述重点介绍了近期使用靶向纳米颗粒治疗癌症的研究，重点关注靶向肿瘤血管（称为“血管靶向”）、肿瘤微环境（“组织靶向”）或单个癌细胞（“细胞靶向”）的方法。本综述还讨论了结合这些不同靶向方法的近期研究。最后，本综述总结了靶向纳米药物领域缺乏临床成功的一些原因。
