Precise control of nanoparticle surface by host–guest chemistry for delivery to tumor

Abstract

Nanoparticles were prepared by host–guest chemistry using stereo-complex formation between right-handed and left-handed helical peptides. The host molecule is a 3rd generation polyamidoamine dendrimer having 16 terminated right-handed helices. Three types of guest molecules were examined: poly(sarcosine)-b-(D-Leu-Aib)₆ (AB-LP), (poly(sarcosine))₃-b-(D-Leu-Aib)₆ (A₃B-LP), and (D-Leu-Aib)₆-b-(poly(sarcosine))₃ (A₃B-apLP). All the guest peptides associate stoichiometrically with the host dendrimer because of the stereo-complex formation. When A₃B-apLP associates with the host dendrimer, the conjugate shows a hydrodynamic diameter of 27 nm, which is explainable by the fact that 16 guest peptides are incorporated in the host dendrimer with tight helix packing and an antiparallel helix dipole arrangement. The nanoparticles were labeled with indocyanine green fluorescence agent and were applied for tumor imaging. Among them, the conjugate with A₃B-apLP shows a long life time in the blood stream and a good tumor/liver signal ratio. Furthermore, the conjugate does not trigger the accelerated blood clearance phenomenon. Although these nanoparticles that were modified by similar guest molecules should have similar surfaces, their in vivo disposition is significantly affected.