Abstract
Cancerous cells and the tumor microenvironment are among key elements involved in cancer development, progression, and resistance to treatment. In order to tackle the cells and the extracellular matrix, we herein propose the use of a class of silica-coated iron oxide nanochains, which have superior magnetic responsiveness and can act as efficient photothermal agents. When internalized by different cancer cell lines and normal (non-cancerous) cells, the nanochains are not toxic, as assessed on 2D and 3D cell culture models. Yet, upon irradiation with near infrared light, the nanochains become efficient cytotoxic photothermal agents. Besides, not only do they generate hyperthermia, which effectively eradicates tumor cells in vitro, but they also locally melt the collagen matrix, as we evidence in real-time, using engineered cell sheets with self-secreted extracellular matrix. By simultaneously acting as physical (magnetic and photothermal) effectors and chemical delivery systems, the nanochain-based platforms offer original multimodal possibilities for prospective cancer treatment, affecting both the cells and the extracellular matrix.
Highlights
Iron oxide nanoparticles (IONPs) are among the most popular and most extensively studied inorganic nanoparticles, which have enabled a series of distinct therapeutic approaches in various biomedical domains [1].Iron oxide nanoparticles were historically used as contrast agents for magnetic resonance imaging (MRI), mostly to detect liver metastases [2]
Less than 1 μm long, anisotropic by shape, and superparamagnetic nanochains were synthesized by magnetic assembly of few (5 ± 1.4) nanoparticle clusters (Figure 1A, Scheme S1)
The size of nanoparticle clusters coated with a 3-nm-thick silica shell was measured from transmission electron microscopy (TEM) micrographs
Summary
Iron oxide nanoparticles (IONPs) are among the most popular and most extensively studied inorganic nanoparticles, which have enabled a series of distinct therapeutic approaches in various biomedical domains [1]. Iron oxide nanoparticles were historically used as contrast agents for magnetic resonance imaging (MRI), mostly to detect liver metastases [2]. IONPs use evolved with the development of MRI-based technologies, enabling the in vivo tracking of single cells [3]. The magnetic responsiveness of IONPs [4] paved the way to magnetic cell manipulation approaches. In order to be useful in biomedicine, nanoparticles should be superparamagnetic. Superparamagnetism is a form of magnetism where magnetization randomly flips at room temperature
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