England Christopher G, Gobin André M, Frieboes Hermann B
Department of Pharmacology & Toxicology, University of Louisville, Louisville, KY 40292, USA; James Graham Brown Cancer Center, University of Louisville, Louisville, KY 40292, USA.
Department of Bioengineering, University of Louisville, Louisville, KY 40292, USA.
Eur Phys J Plus. 2015 Nov 1;130(11). doi: 10.1140/epjp/i2015-15231-1. Epub 2015 Nov 19.
Although nanotherapeutics offer a targeted and potentially less toxic alternative to systemic chemotherapy in cancer treatment, nanotherapeutic transport is typically hindered by abnormal characteristics of tumor tissue. Once nanoparticles targeted to tumor cells arrive in the circulation of tumor vasculature, they must extravasate from irregular vessels and diffuse through the tissue to ideally reach all malignant cells in cytotoxic concentrations. The enhanced permeability and retention effect can be leveraged to promote extravasation of appropriately sized particles from tumor vasculature; however, therapeutic success remains elusive partly due to inadequate intra-tumoral transport promoting heterogeneous nanoparticle uptake and distribution. Irregular tumor vasculature not only hinders particle transport but also sustains hypoxic tissue kregions with quiescent cells, which may be unaffected by cycle-dependent chemotherapeutics released from nanoparticles and thus regrow tumor tissue following nanotherapy. Furthermore, a large proportion of systemically injected nanoparticles may become sequestered by the reticuloendothelial system, resulting in overall diminished efficacy. We review recent work evaluating the uptake and distribution of gold nanoparticles in pre-clinical tumor models, with the goal to help improve nanotherapy outcomes. We also examine the potential role of novel layered gold nanoparticles designed to address some of these critical issues, assessing their uptake and transport in cancerous tissue.
尽管纳米疗法在癌症治疗中为全身化疗提供了一种靶向性且潜在毒性较低的替代方案，但纳米治疗药物的运输通常会受到肿瘤组织异常特性的阻碍。一旦靶向肿瘤细胞的纳米颗粒进入肿瘤脉管系统的循环中，它们必须从不规则的血管渗出并扩散穿过组织，以理想地达到细胞毒性浓度从而作用于所有恶性细胞。增强的渗透和滞留效应可用于促进适当大小的颗粒从肿瘤脉管系统渗出；然而，治疗成功仍然难以实现，部分原因是肿瘤内运输不足，导致纳米颗粒摄取和分布不均。不规则的肿瘤脉管系统不仅阻碍颗粒运输，还维持着含有静止细胞的缺氧组织区域，这些细胞可能不受纳米颗粒释放的周期依赖性化疗药物的影响，从而在纳米治疗后使肿瘤组织再生。此外，大部分经全身注射的纳米颗粒可能会被网状内皮系统截留，导致整体疗效降低。我们回顾了最近在临床前肿瘤模型中评估金纳米颗粒摄取和分布的工作，目的是帮助改善纳米治疗效果。我们还研究了旨在解决其中一些关键问题的新型层状金纳米颗粒的潜在作用，评估它们在癌组织中的摄取和运输情况。
