Investigation of Melphalan interaction as an alkylating agent with nucleotides by using surface enhanced Raman spectroscopy (SERS).

SERS (Surface Enhanced Raman Spectroscopy) is a new Raman spectroscopy which relies on Surface Plasmon Resonance (SPR) of metal nanoparticles. We have applied colloidal silver and gold nanoparticles as amplifier agents to enhance nucleotide Raman signals. It is observed that without these enhancing agents, it is impossible to investigate nucleotide spectrum due to weak Raman signals. Interaction mechanism of Melphalan, an anticancer drug with four nucleotides (Adenine, Cytosine, Guanine, Thymine) was investigated using SERS to detect and identify changes due to alkylating process in Raman spectra. After incubating Melphalan drug with nucleotides for 24 h at 37 °C, some changes occurred in SERS spectrum and interpretation of SERS spectra revealed the influence of the alkyl substitution on peaks and Raman shifts. After incubation of Melphalan with each nucleotide, intensity of relevant SERS signals assigned to Amid III group of Cytosine and Amid I of Thymine decreased significantly, confirming alkylating taking place. In this study, we also investigated the effect of nanoparticles type on nucleotide spectrum. We could not obtain useful information in the cases of guanine nucleotide. The SERS spectrum of Cytosine as an example of nucleotides in aqueous solution compared to solid state and results demonstrated that in solid state better signals were obtained than in liquid state.

A modeling study of the effect of an alternating magnetic field on magnetite nanoparticles in proximity of the neuronal microtubules: A proposed mechanism for detachment of tau proteins.

BACKGROUND AND OBJECTIVE: It is known that the disintegration of microtubules in neurons occurs in response to the phosphorylation of the tau proteins that promotes the structural instability of the microtubules, as one of the factors underlying the onset of Alzheimer's disease (AD). METHODS: In this study, the mechanical variations undergone by the tau protein's and microtubule's structures due to the action of intrinsic magnetite nanoparticles inside the brain tissue have been computationally modeled using the finite element (FEM) method. RESULTS: The von Mises stress induced by magnetite nanoparticles, subject to an applied alternating magnetic field, leads to local heating and mechanical forces, prompting a corresponding deformation in, and displacement of, the microtubule and the tau protein. CONCLUSIONS: The induction of these deformations would increase the probability of the microtubules' depolymerization, and hence their eventual structural disintegration.