Light- and Melanin Nanoparticle-Induced Cytotoxicity in Metastatic Cancer Cells

光和黑色素纳米粒子诱导转移性癌细胞的细胞毒性

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作者:Victoria R Gabriele, Robabeh M Mazhabi, Natalie Alexander, Purna Mukherjee, Thomas N Seyfried, Njemuwa Nwaji, Eser M Akinoglu, Andrzej Mackiewicz, Guofu Zhou, Michael Giersig, Michael J Naughton, Krzysztof Kempa

Abstract

Melanin nanoparticles are known to be biologically benign to human cells for a wide range of concentrations in a high glucose culture nutrition. Here, we show cytotoxic behavior at high nanoparticle and low glucose concentrations, as well as at low nanoparticle concentration under exposure to (nonionizing) visible radiation. To study these effects in detail, we developed highly monodispersed melanin nanoparticles (both uncoated and glucose-coated). In order to study the effect of significant cellular uptake of these nanoparticles, we employed three cancer cell lines: VM-M3, A375 (derived from melanoma), and HeLa, all known to exhibit strong macrophagic character, i.e., strong nanoparticle uptake through phagocytic ingestion. Our main observations are: (i) metastatic VM-M3 cancer cells massively ingest melanin nanoparticles (mNPs); (ii) the observed ingestion is enhanced by coating mNPs with glucose; (iii) after a certain level of mNP ingestion, the metastatic cancer cells studied here are observed to die-glucose coating appears to slow that process; (iv) cells that accumulate mNPs are much more susceptible to killing by laser illumination than cells that do not accumulate mNPs; and (v) non-metastatic VM-NM1 cancer cells also studied in this work do not ingest the mNPs, and remain unaffected after receiving identical optical energy levels and doses. Results of this study could lead to the development of a therapy for control of metastatic stages of cancer.

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