Fu Lu, Yong Joel M, Yeh Robyn, Bartlett Florence, Whitelock John M, Lord Megan S
Graduate School of Biomedical Engineering, University of New South Wales, Sydney, NSW, 2052, Australia.
Katherina Gaus Light Microscopy Facility, Mark Wainwright Analytical Centre, University of New South Wales, Sydney, NSW, 2052, Australia.
Adv Healthc Mater. 2025 May;14(12):e2405129. doi: 10.1002/adhm.202405129. Epub 2025 Mar 20.
Angiogenesis is a crucial step in tumor progression, including melanoma, making anti-angiogenic strategies a widely explored treatment approach. However, both innate and acquired resistance to these therapies suggest that this approach may need re-evaluation. Nanoparticles have gained attention for their potential to enhance drug delivery and retention within tumors via the bloodstream. However, the in vitro screening of nanoparticles is limited by the inability of preclinical models to replicate the complex tumor microenvironment, especially the blood supply. Here, it is demonstrated that melanoma cells embedded in Matrigel spheroids can engraft in and be vascularized by the chorioallantoic membrane (CAM) of fertilized chicken eggs. This model allows for the assessment of nanoparticle toxicity and accumulation in tumor spheroids, as well as functional effects such as angiogenesis. Cerium oxide nanoparticles (nanoceria) and their surface functionalized derivatives are widely explored for biomedical applications due to their ability to modulate oxidative stress and angiogenesis. Here, it is observed that heparin functionalized nanoceria penetrate melanoma spheroids in the CAM and promote spheroid vascularization to a greater extent than nanoceria alone. This study aids in the development of preclinical cancer models for nanoparticle screening and provides new insight into the interplay between nanoparticle surface coatings and biological effects.
血管生成是肿瘤进展（包括黑色素瘤）中的关键步骤，这使得抗血管生成策略成为一种广泛探索的治疗方法。然而，对这些疗法的先天性和获得性耐药性表明，这种方法可能需要重新评估。纳米颗粒因其通过血液循环增强药物在肿瘤内递送和滞留的潜力而受到关注。然而，纳米颗粒的体外筛选受到临床前模型无法复制复杂肿瘤微环境（尤其是血液供应）的限制。在此，证明了嵌入基质胶球体中的黑色素瘤细胞可以植入受精鸡蛋的绒毛尿囊膜（CAM）并在其中血管化。该模型允许评估纳米颗粒在肿瘤球体中的毒性和积累，以及诸如血管生成等功能效应。氧化铈纳米颗粒（纳米铈）及其表面功能化衍生物因其调节氧化应激和血管生成的能力而被广泛用于生物医学应用。在此，观察到肝素功能化纳米铈比单独的纳米铈更能穿透CAM中的黑色素瘤球体并促进球体血管化。这项研究有助于开发用于纳米颗粒筛选的临床前癌症模型，并为纳米颗粒表面涂层与生物学效应之间的相互作用提供了新的见解。
