Hiroaki Shimomoto

Multi-functional liposomes having temperature-triggered release and magnetic resonance imaging for tumor-specific chemotherapy.

For development of tumor-specific chemotherapy, we designed liposomes with temperature-triggered drug release and magnetic resonance imaging (MRI) functions. We prepared multi-functional liposomes by incorporating thermosensitive poly(2-ethoxy(ethoxyethyl)vinyl ether) chains with a lower critical solution temperatures around 40 °C and polyamidoamine G3 dendron-based lipids having Gd(3+) chelate residues into pegylated liposomes. These stable doxorubicin (DOX)-loaded liposomes retained DOX in their interior below physiological temperature but released DOX immediately at temperatures greater than 40 °C. They exhibited excellent ability to shorten the longitudinal proton relaxation time. When administered intravenously into colon 26 tumor-bearing mice, accumulated liposomes in tumors increased with time, reaching a constant level 8 h after administration by following T(1)-weighted MRI signal intensity in tumors. Liposome size affected the liposome accumulation efficiency in tumors: liposomes of about 100 nm diameter were accumulated more efficiently than those with about 50 nm diameter. Tumor size also affected accumulation: more efficient accumulation occurred in larger tumors. Tumor growth was strongly suppressed when liposomes loaded with DOX were administered intravenously into tumor-bearing mice and the tumor was heated mildly at 44 °C for 10 min at 8 h after administration. Multi-functional liposomes having temperature-triggered drug release and MRI functions might engender personalized chemotherapy, providing efficient patient-optimized chemotherapy.

Synthesis of polymers with densely-grafted oligo(ethylene glycol)s by Pd-initiated polymerization of oxyethylene-containing diazoacetates

Synthesis and characterization of polymers with densely-grafted oligo(ethylene glycol)s (OEGs) are described. Polymerization of OEG-containing diazoacetates with (η3-C3H5)PdCl-based initiating systems afforded C–C main chain polymers bearing OEGs on each main chain carbon atom. The polymers with a short OEG side chain showed a lower critical solution temperature-type phase separation in an aqueous medium; the transition temperatures were higher than those of the corresponding vinyl polymers with the same oxyethylene chain length. In addition, the Li-ion conductivity was examined to reveal that the polymers with densely-grafted OEGs showed higher values than the corresponding vinyl polymers, despite the fact that no significant difference in the glass transition temperature was observed between the two types of polymers.

Polymerization of alkyl diazoacetates initiated by the amidinate/Pd system: efficient synthesis of high molecular weight poly(alkoxycarbonylmethylene)s with moderate stereoregularity

The initiating ability of a new system, amidinate/Pd, for the polymerization of diazoacetates is described. The system is effective in affording relatively high number-average molecular weight (Mn) polymers from ethyl diazoacetate (EDA, e.g., Mn = 45 100, 44% yield) and methyl diazoacetate (MDA, e.g., Mn = 26 200, 56% yield) in moderate yield. The polymerization of n-hexyl diazoacetate (nHDA) and benzyl diazoacetate (BDA) by the amidinate/Pd system yields high Mn polymers (Mn = ca.100 000), although the yield was below 10%. The system is also effective in the copolymerization of EDA with nHDA, BDA, and cyclohexyldiazoacetate (cHDA), affording high Mn copolymers in moderate yield. NMR spectra of the products obtained with the system suggest that the polymerization proceeds with significantly higher stereoregularity compared to that with previously reported Pd-based initiating systems.