Cell-Modulating Effect of Poly(Aspartic Acid) and Its Complex with Cationic Polyaspartamide

In this communication, poly(aspartic acid) (pAsp), its fluorescently labeled conjugate with lucifer yellow ethylenediamine (pAsp-LY), and 2,2-dimethyl-1,3-propanediamine-derived cationic polyaspartamide (pDmpa) were synthesized by liquid-phase method. Octamer of L-aspartic acid (L-Asp(8)) was also obtained by solid-phase synthesis. pDmpa interacted with both pAsp and model plasmid DNA to form compact nanosized interpolymer complexes, which showed different colloidal properties. Effective cellular uptake of pAsp-LY by NIH 3T3 fibroblasts was detected by confocal microscopy. Pre-complexation of pAsp-LY with pDmpa did not noticeably increase intracellular accumulation of the conjugate. Both pAsp and L-Asp(8) were found to increase viability of murine 3T3 cells and human skin fibroblasts at mu g/mL concentrations according to the MTT assay (24 h). This effect was observed along with moderate prooxidant activity of the peptides in the cells according to the DCFDA fluorescence assay. The results suggest that aspartic acid-based peptides per se are capable of penetrating mammalian cells and affecting their metabolic activity. The peptides can be complexed with their cationic derivative, i.e., pDmpa polyaspartamide, to develop nanosized formulations of pAsp and its conjugates.