Self-assembled nanoparticle of poly(amino acid)s and their application to cancer therapy

Abstract

Novel amphiphilic graft copolymers composed of poly(2-hydroxyethyl aspartamide) (PHEA) as the hydrophilic backbone and oligo(L-leucine) as the grafted hydrophobic chain were successfully synthesized by a ring-opening polymerization of the Leu-NCA to backbone polymer. The molecular structure of PHEA-g-OLleu, i.e. DS(Degree of substitution), and DP(degree of polymerization) was determined with the peak intensity in $^1H-NMR$ spectra and the weight percentage of the element in EA(elemental analysis). The DS is the mole percentage of the grafting unit with oligo(L-leucin) per total succinimide unit. DS can be controlled by grafting of ethylenediamine onto the PHEA backbone to prepare various macroinitiator, $PHEA-NH_2$. The PD is the degree of polymerization of oligo(L-leucine) onto PHEA backbone polymer. Resulting copolymers were characterized by various analytical techniques including differential scanning calorimeter, thermogravimetric analysis and X-ray diffractometry. These results obtained could prove that the spatial confinement of the oligo(L-leucine) grafts facilitated the crystallization of oligo(L-leucine) domains with neighboring oligo(L-leucine) in the PHEA backbone. The amphiphilic graft copolymer formed nano-sized self-assemblies with unique morphology in aqueous solution. The hydrophobic domains can adopt regular conformations that are insoluble in water, namely, rod-like α-helices for oligo(L-leucine). The unique self-assemblies in aqueous solution as the degree of substitution (DS) were observed with dynamic light scattering (DLS), fluorescence spectroscopy, circular dichroism (CD), transmission electron microscopy (TEM), Langmuir Blodgett (LB), and small angle neutron scattering (SANS) measurements. At the high DS, backbone PHEA could not form easily the loop and then another structure would be formed. Appropriate looping units of hydrophilic backbone polymer and curvature, K are essential factors to form the stable self-assembled aggregates. Al...