Valente Karolina P, Suleman Afzal, Brolo Alexandre G
Department of Mechanical Engineering, University of Victoria, 3800 Finnerty Road, Victoria, British Columbia V8P 5C2, Canada.
Centre for Advanced Materials and Related Technology, University of Victoria, 3800 Finnerty Road, Victoria, British Columbia V8P 5C2, Canada.
ACS Appl Bio Mater. 2020 Oct 19;3(10):6992-7002. doi: 10.1021/acsabm.0c00872. Epub 2020 Sep 25.
Gold nanoparticles have emerged as a prominent tool in nanomedicine, particularly for applications in cancer diagnostic and treatment. One of the challenges for the successful implementation of gold nanoparticles in cancer therapy is their delivery to the specific cancer area within the tumor microenvironment. The presence of cancer enables a poorly organized vascularization system, increasing the pressure with the microenvironment, limiting the uptake of particles. The physicochemical properties of the gold nanoparticles (size, shape, and surface charge) also have a significant effect on diffusion to the tumor site and cellular uptake. In this work, we analyzed the transport of 10 nm gold nanoparticles with different surface charges (neutral, negative, and positive) through a hydrogel composite. Three-dimensional in vitro models composed of breast cancer cells loaded in the hydrogel composite were used for the qualitative and quantitative evaluation of cellular uptake of the gold nanoparticles. Surprisingly, an inverse correlation between the diffusion coefficients of the nanoparticles and cellular uptake was demonstrated. Positively charged gold nanoparticles displayed high cellular uptake, although their diffusion coefficient indicated slow transport through the hydrogel matrix. Neutral particles, on the other hand, displayed fast diffusion but the lowest cellular uptake. The results obtained indicate that nanoparticle diffusion and cellular uptake should be studied together in realistic in vitro models for a true evaluation of transport in tumor microenvironments.
金纳米颗粒已成为纳米医学中的一种重要工具，尤其在癌症诊断和治疗方面的应用。在癌症治疗中成功应用金纳米颗粒面临的挑战之一是将其递送至肿瘤微环境中的特定癌症区域。癌症的存在导致血管生成系统紊乱，增加了微环境中的压力，限制了颗粒的摄取。金纳米颗粒的物理化学性质（尺寸、形状和表面电荷）也对扩散到肿瘤部位和细胞摄取有显著影响。在这项工作中，我们分析了具有不同表面电荷（中性、负性和正性）的10纳米金纳米颗粒通过水凝胶复合材料的传输情况。由负载在水凝胶复合材料中的乳腺癌细胞组成的三维体外模型用于定性和定量评估金纳米颗粒的细胞摄取。令人惊讶的是，证明了纳米颗粒的扩散系数与细胞摄取之间存在负相关。带正电荷的金纳米颗粒显示出高细胞摄取，尽管其扩散系数表明通过水凝胶基质的传输缓慢。另一方面，中性颗粒显示出快速扩散但细胞摄取最低。获得的结果表明，在真实的体外模型中应同时研究纳米颗粒扩散和细胞摄取，以真正评估肿瘤微环境中的传输情况。
