Synthesis and evaluation of a novel 2',5'-bridged nucleic acid with sugar conformation fixed to S-type by N-O linkage.

Our work involves the design and synthesis of various types of bridged nucleic acid (BNA). Here, we describe a novel 2'-O, 5'-N-bridged nucleic acid, 2',5'-BNA(ON), whose sugar puckering is fixed to the S-type conformation by N-O linkage. A 2',5'-BNA(ON)-containing dimer unit was synthesized via a coupling reaction between a protected 2',5'-BNA(ON)-U monomer and a thymidine derivative.

Polycation liposome enhances the endocytic uptake of photosensitizer into cells in the presence of serum.

To construct a novel drug delivery carrier that possesses high therapeutic efficacy with low dosage, we designed polyethylenimine-modified liposome (polycation liposome, PCL) and examined the entrapment of photosensitizer, benzoporphyrin derivative monoacid ring A (BPD-MA), for antiangiogenic photodynamic therapy (PDT). Photosensitizer entrapped in PCLs showed enhanced phototoxicity for a human vascular endothelial cell line, ECV304, in comparison with that for nonmodified control liposome. Interestingly, phototoxicity of control liposomal BPD-MA was suppressed in the presence of serum, but PCL maintained the phototoxicity in the presence of serum following PCL-mediated PDT treatment due to the stability of PCL and the reduced detachment of encapsulated photosensitizer from liposome to serum.

Polycation liposome-mediated gene transfer in vivo.

The polycation liposome (PCL), a recently developed gene transfer system, is simply prepared by a modification of liposomes with cetylated polyethylenimine (PEI), and shows remarkable transgene efficiency with low cytotoxicity. In the present study, we investigated the applicability of PCLs for in vivo gene transfer, since the PCL-mediated transgene efficiency was found to be maintained in the presence of serum. PCLs composed of dioleoylphosphatidylethanolamine (DOPE) with 5 mol% cetyl PEI (PEI average mr.