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Published on: May 18, 2018
Functionalized Cerium Oxide Nanoparticles Enhance Penetration into Melanoma Spheroids In Vivo through Angiogenesis
Lu Fu1, Joel M Yong1, Robyn Yeh1
1Graduate School of Biomedical Engineering, University of New South Wales, Sydney, NSW, 2052, Australia.
Abstract:
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.
Insights
This study introduces a new chick embryo model for testing anti-cancer nanoparticles. Heparin-coated cerium oxide nanoparticles effectively target melanoma and enhance tumor vascularization, offering a promising therapeutic strategy.
Area of Science:
- Oncology
- Nanomedicine
- Developmental Biology
Background:
- Angiogenesis is vital for tumor growth, but resistance to anti-angiogenic therapies necessitates new approaches.
- Nanoparticles offer enhanced drug delivery, yet in vitro models struggle to replicate the tumor microenvironment.
- Preclinical models are needed to evaluate nanoparticle efficacy and tumor interactions.
Purpose of the Study:
- To develop a novel chick embryo model for assessing nanoparticle-based cancer therapies.
- To investigate the efficacy of cerium oxide nanoparticles (nanoceria) and their derivatives in targeting melanoma.
- To explore the impact of nanoparticle surface functionalization on tumor vascularization and drug delivery.
Main Methods:
- Melanoma cells were cultured as spheroids and engrafted onto the chorioallantoic membrane (CAM) of fertilized chicken eggs.
- The CAM model was used to assess nanoparticle toxicity, accumulation, and effects on tumor vascularization.
- Heparin-functionalized nanoceria were compared to unmodified nanoceria for their effects on melanoma spheroids.
Main Results:
- The CAM model successfully supported melanoma spheroid engraftment and vascularization.
- Heparin-functionalized nanoceria demonstrated enhanced penetration into melanoma spheroids compared to unmodified nanoceria.
- Heparin-functionalized nanoceria significantly promoted spheroid vascularization, exceeding the effects of unmodified nanoceria.
Conclusions:
- The chick embryo CAM model provides a viable platform for preclinical nanoparticle screening.
- Surface functionalization of nanoceria, specifically with heparin, can improve their tumor targeting and therapeutic effects.
- This research offers insights into nanoparticle-host interactions and guides the development of advanced nanomedicines for melanoma treatment.
