| 摘要 |
Among natural mechanisms of cell deaths, disease or toxicity, one of the most common method is through overloading of certain biological metals such as calcium, iron and zinc. We propose to utilize this natural mechanism of cell death against cancer by utilizing the well known phenomenon of enhanced permeation and retention effect (EPR effect) and metal-binding nanoparticle moieties that can self-degrade under certain biological conditions such as pH. More specifically, we show that one can form nanoparticles that consist of polymerized citric acid and various different types of metals including, but not limited to, iron, calcium, zinc, silver and magnesium, displaying acid-stability and self-degradation leading to constituent metal release when pH rises closer to the neutral pH of 7 or higher. We also show that these nanoparticles with different metal compositions have distinct cytotoxicity against various different types of cancer cell lines, including B16F10 melanoma, H460 human lung cancer, T98G kidney cancer, Ramos leukemic cancer, etc. in vitro. We also show evidence of in vivo anti-cancer activity of our nanoparticles containing various different metals using mouse model studies.
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