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.
Highlights
We have developed highly monodispersed glucose-coated melanin nanoparticles, and have used these to reveal massive NP uptake by the three cancer cell lines, VM-M3, A375, and HeLa, which confirm these cell types’ macrophagic character
To estimate the photothermal response of the in-blood circulating tumor cells sensitized with melanin nanoparticles (mNPs), we modeled the cell as a water droplet with average radius rc ≈ 5 × 10−6 m, immersed in blood serum, which for simplicity is modeled as water, with thermal conductivity km = 0.6 W·K−1 ·m−1, specific heat cw = 4186 J·kg−1 ·K−1, and density ρw = 1000 kg·m−3
We found that the level of radiation capable of catastrophically destroying mNPfilled VM-M3 cells, like in Figure 5, is safe for VM-M3 cells not sensitized with mNPs
Summary
The emergence of nanoparticle (NP) technology in biomedicine has led to many applications [1,2]. These include tumor imaging and targeting [3], tissue engineering [4], drug delivery [5], tumor destruction [6], pathogen detection [7], and protein detection [8], among others. Small nonpolar NPs can cross biological barriers and translocate across cells, tissues, and organs [9]. The internalization process of NPs by cells is a key factor in determining their biomedical function, toxicity, and biodistribution [11].
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