Challenges associated with Penetration of Nanoparticles across Cell and Tissue Barriers: A Review of Current Status and Future Prospects.
Challenges associated with Penetration of Nanoparticles across Cell and Tissue Barriers: A Review of Current Status and Future Prospects.
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DOI：
10.1016/j.nantod.2014.04.008
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发表时间：
2014-04-01
期刊：
影响因子：
17.4
通讯作者：
Mitragotri S
中科院分区：
文献类型：
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作者：
Barua S;Mitragotri S
纳米颗粒（NP）已成为治疗癌症、心血管疾病和炎症性疾病等多种疾病的有效方式。各种形式的纳米颗粒，包括脂质体、聚合物颗粒、胶束、树枝状聚合物、量子点、金纳米颗粒和碳纳米管，已被合成并测试用于治疗应用。限制纳米颗粒成功的最大挑战之一是它们能够以必要的剂量到达治疗部位，同时最大限度地减少在不需要的部位的积累。纳米粒子的生物分布是由人体的生物屏障决定的，这些屏障以几种不同的方式表现出来。对于纳米粒子的血管内递送，屏障表现为：（i）肝脏和脾脏中的免疫清除，（ii）穿过内皮渗透到靶组织，（iii）穿过组织间质，（iv）靶细胞中的内吞作用，（v）通过细胞质扩散，以及（vi）最终进入细胞核（如果需要）。纳米粒子的某些应用还依赖于通过替代途径的递送，包括皮肤和鼻粘膜、肺、肠和阴道。在这些情况下，这些组织的扩散阻力对输送构成了重大障碍。本综述重点关注目前对纳米颗粒穿透生物屏障的理解。重点是运输障碍而不是免疫障碍。该评论还讨论了克服阻隔性能的设计策略。
Nanoparticles (NPs) have emerged as an effective modality for the treatment of various diseases including cancer, cardiovascular and inflammatory diseases. Various forms of NPs including liposomes, polymer particles, micelles, dendrimers, quantum dots, gold NPs and carbon nanotubes have been synthesized and tested for therapeutic applications. One of the greatest challenges that limit the success of NPs is their ability to reach the therapeutic site at necessary doses while minimizing accumulation at undesired sites. The biodistribution of NPs is determined by body’s biological barriers that manifest in several distinct ways. For intravascular delivery of NPs, the barrier manifests in the form of: (i) immune clearance in the liver and spleen, (ii) permeation across the endothelium into target tissues, (iii) penetration through the tissue interstitium, (iv) endocytosis in target cells, (v) diffusion through cytoplasm and (vi) eventually entry into the nucleus, if required. Certain applications of NPs also rely on delivery through alternate routes including skin and mucosal membranes of the nose, lungs, intestine and vagina. In these cases, the diffusive resistance of these tissues poses a significant barrier to delivery. This review focuses on the current understanding of penetration of NPs through biological barriers. Emphasis is placed on transport barriers and not immunological barriers. The review also discusses design strategies for overcoming the barrier properties.