Unsymmetric vesicles with a different design on each side for near-infrared fluorescence imaging of tumor tissues

Abstract

Spherical vesicular assemblies with unsymmetric membranes are prepared from A₃B-type and AB′-type peptides with different helix senses in the hydrophobic B and B′ blocks under the control of three associated factors: stereo-complex formation, dipole–dipole interactions, and steric effects. [(Sar)₂₆]₃-b-(L-Leu-Aib)₆ (A₃BL), (Sar)₂₇-b-(L-Leu-Aib)₆ (ABL), (Sar)₂₈-b-(D-Leu-Aib)₆ (ABD), lipoic-acid terminated ABL (lipoABL), and lipoic-acid terminated ABD (lipoABD) are mixed while keeping equimolar ratios of the total amounts of the right- and the left-handed helices. When A₃BL exceeds more than 60% of all the right-handed helices of the mixture, the unsymmetric vesicles are formed, as indicated by the selective adsorption of gold nanoparticles on the vesicle surface observed by TEM. The unsymmetric vesicles are also prepared using ICGABL and ICGABD with a near-infrared fluorophore, indocyanine green (ICG), at the terminals of ABL and ABD. The unsymmetric vesicle formation is verified by fluorescence quenching with the addition of In ions to the solution. When these vesicles are injected into tumor-bearing mice, the vesicles are effectively accumulated into tumor tissues via the EPR effect. The unsymmetric vesicle containing ICG at the inward surface induces less IgM production than that with ICG at the outward surface. More stealth vesicles in the blood stream are therefore obtainable by concealing the imaging fluorophores in the vesicle.