Masaru Mukai

Photodynamic Activity of C70 Caged within Surface‐Cross‐Linked Liposomes

[70]Fullerene (C(70)) encapsulated into a surface-cross-linked liposome, a so-called cerasome, was prepared by an exchange reaction incorporating C(70)gamma-cyclodextrin complexes into lipid membranes. Fullerene exchange in a cerasome-incorporated C(70) (CIC(70)), as well as in a lipid-membrane-incorporated C(70) (LMIC(70)), was completed within 1 min with stirring at 25 degrees C. CIC(70) was more resistant to lysis than LMIC(70) towards lysing agents such as surfactants. Furthermore, the photodynamic activity of CIC(70) in HeLa cells was similar to that of LMIC(70), indicating that C(70) can act as a photosensitizing drug (PS) without release from cerasome membranes. Thus, in contrast with general drug-delivery systems (DDSs), which require the drug to be released from the interior of liposomes, carriers for PSs for use in photodynamic therapy (PDT) do not necessarily need to release the drug. These results indicate that DDSs with high morphological stability can increase the residence time in blood and achieves tumor-selective drug delivery by the enhanced permeability and retention (EPR) effect.

Propagation and amplification of molecular information using a photoresponsive molecular switch

Molecular communication is a bio-inspired communication paradigm using molecules as information carriers. The molecular communication system includes propagation of information carrier molecules between a molecular sender and a molecular receiver and followed by amplification of the information at the receiver. In this article, we built an example molecular communication system using a gemini peptide lipid as a molecular switch. The molecular switch embedded in the lipid bilayer membranes exhibited photoresponsive recognition behaviour towards metal ions, such as Cu2+ and Zn2+, to control propagation of molecular capsules formed by small liposomes to a giant liposomal receiver. In addition, the molecular switch acted as an artificial receptor in the receiver, receiving a photonic signal to communicate with an enzyme as a signal amplifier by using Cu2+ ion as a mediator between the receptor and the amplifier.

Solvent-chirality selective organogelation by chiral aspartame lipids

We examined supramolecular gelation of propylene carbonate enantiomers with novel chiral aspartame lipids. Different gelation ability and stability were observed based on the combination of gelator and the solvent enantiomers. This work demonstrates that gelator–solvent chirality matching can determine self-assembled nanostructures and gelation efficiency.

A hydro/organo/hybrid gelator: a peptide lipid with turning aspartame head groups.

This work presents a novel bola-type peptide lipid which can gelate water, organic solvents, and water/organic-solvent mixtures. In its molecular structure, an amphiphilic dipeptide aspartame (L-α-aspartyl-L-phenylalanine methyl ester) is connected at both ends of an alkylene linker. The different morphologies in the hydrogel (helical nanotapes) and the organogel (tape-like nanostructures) were visualized by energy-filtering transmission electron microscopy (EF-TEM) and energy-filtering scanning electron microscopy (FE-SEM), and the molecular arrangement was examined using X-ray diffraction (XRD), infrared (IR) spectroscopy, and circular dichroism (CD) spectroscopy. Possessing a hydrophilic aspartic acid group and a (relatively) hydrophobic phenylalanine methyl ester group, the dipeptide head group can turn about in response to solvent polarity. As a consequence, the solvent condition changed the molecular packing of the gelator and affected the overall supramolecular structure of the gel. It is noted that the peptide lipid gelated mixed solvents of water and organic solvents such as dichloromethane, liquid-paraffin, olive-oil, silicone-oils, and so on. The present hybrid gel can simultaneously hold hydrophilic and hydrophobic functional materials.

Intermolecular communication on a liposomal membrane: enzymatic amplification of a photonic signal with a gemini peptide lipid as a membrane-bound artificial receptor.

A supramolecular system that can activate an enzyme through photo-isomerization was constructed by using a liposomal membrane scaffold. The design of the system was inspired by natural signal transduction systems, in which enzymes amplify external signals to control signal transduction pathways. The liposomal membrane, which provided a scaffold for the system, was prepared by self-assembly of a photoresponsive receptor and a cationic synthetic lipid. NADH-dependent L-lactate dehydrogenase, the signal amplifier, was immobilized on the liposomal surface by electrostatic interactions. Recognition of photonic signals by the membrane-bound receptor induced photo-isomerization, which significantly altered the receptors metal-binding affinity. The response to the photonic signal was transmitted to the enzyme by Cu(2+) ions. The enzyme amplified the chemical information through a catalytic reaction to generate the intended output signal.

Fusion-Triggered Switching of Enzymatic Activity on an Artificial Cell Membrane

A nanosensory membrane device was constructed for detecting liposome fusion through changes in an enzymatic activity. Inspired by a biological signal transduction system, the device design involved functionalized liposomal membranes prepared by self-assembly of the following molecular components: a synthetic peptide lipid and a phospholipid as matrix membrane components, a Schiffs base of pyridoxal 5′-phosphate with phosphatidylethanolamine as a thermo-responsive artificial receptor, NADH-dependent L-lactate dehydrogenase as a signal amplifier, and Cu2+ ion as a signal mediator between the receptor and enzyme. The enzymatic activity of the membrane device was adjustable by changing the matrix lipid composition, reflecting the thermotropic phase transition behavior of the lipid membranes, which in turn controlled receptor binding affinity toward the enzyme-inhibiting mediator species. When an effective fusogen anionic polymer was added to these cationic liposomes, membrane fusion occurred, and the functionalized liposomal membranes responded with changes in enzymatic activity, thus serving as an effective nanosensory device for liposome fusion detection.

Molecular communication on artificial cell membranes

Molecular communication is a bio-inspired communication paradigm using molecules as information carriers. In this paper, we built an example molecular communication system in aqueous media, which includes propagation of molecular capsules capable of carrying molecular information between a molecular sender and a molecular receiver and followed amplification of the information at the receiver. A gemini peptide lipid as a molecular switch embedded in the lipid bilayer membranes logically controlled propagation of molecular capsules formed with small liposomes from a sender to a receiver each composed of a giant liposome, with input signals, such as chemical, photonic, and thermal signals. In addition, the molecular switch acted as an artificial receptor at the receiver, receiving a photonic signal to communicate with an enzyme as a signal amplifier by using Cu2+ ion as a mediator between the receptor and the amplifier.