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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.

Keywords:
melanoma, melanin nanoparticles, cytotoxicity, laser medical applications, hyperthermia

Abstract:
We study the large-amplitude response of classical molecules to electromagnetic radiation, showing the universality of the transition from linear to nonlinear response and breakup at sufficiently large amplitudes. We demonstrate that a range of models, from the simple harmonic oscillator to the successful Peyrard-Bishop-Dauxois type models of DNA, which include realistic effects of the environment (including damping and dephasing due to thermal fluctuations), lead to characteristic universal behavior: formation of domains of dissociation in driving force amplitude-frequency space, characterized by the presence of local boundary minima. We demonstrate that by simply following the progression of the resonance maxima in this space, while gradually increasing intensity of the radiation, one must necessarily arrive at one of these minima, i.e., a point where the ultrahigh spectral selectivity is retained. We show that this universal property, applicable to other oscillatory systems, is a consequence of the fact that these models belong to the fold catastrophe universality class of Thom's catastrophe theory. This in turn implies that for most biostructures, including DNA, high spectral sensitivity near the onset of the denaturation processes can be expected. Such spectrally selective molecular denaturation could find important applications in biology and medicine.