No abstract

Dendron lipids designed to consist of amine-terminated polyamidoamine G1 dendron and two octadecyl chains were used for the preparation of pH-responsive molecular assemblies having phase structures that are changed through their dynamic molecular shape. The dendron lipid contains two primary amines and two tertiary amines in the dendron moiety, changing its charged state in the pH region between pH 10 and pH 4. The assemblies were shown to take a vesicle structure at neutral and alkaline pHs, but their structure changed to a micelle-like structure below pH 6.4. Because this pH region corresponds to one in which tertiary amines of the dendron lipid became protonated, protonation of tertiary amines in addition to primary amines in the dendron moiety might affect its dynamic molecular shape, resulting in a sharp pH response of the assemblies. The assemblies tended to form aggregates when taking on a vesicle form with a gel phase, but incorporation of a poly(ethylene glycol)-lipid provided dendron lipid vesicles with both sharp pH response and high colloidal stability. The poly(ethylene glycol)-incorporated dendron lipid vesicles tightly retained ovalbumin molecules in their internal aqueous space but released them almost completely at pH 6.0. In addition, the vesicles were shown to achieve efficient ovalbumin delivery into cytosol of DC2.4 cells (mouse dendritic cell line) after internalization through endocytosis.

The use of skin environment-sensitive liposomes for transdermal penetration is beneficial for improving cosmetic efficacy.

Sonodynamic therapy (SDT) is a novel promising noninvasive therapy involving utilization of low‐intensity ultrasound and sonosensitizer, which can generate reactive oxygen species (ROS) by sonication. In SDT, a high therapeutic effect is achieved by intracellular delivery and accumulation at the target sites of sonosensitizer followed by oxidative damage of produced ROS by sonication. Here, pH‐ and redox‐responsive hollow nanocapsules are prepared through the introduction of disulfide cross‐linkages to self‐assembled polymer vesicles formed from polyamidoamine dendron‐poly(l‐lysine) for the efficient delivery of sonosensitizer. As sonosensitizer, doxorubicin (DOX), an anticancer drug accumulating into cell nucleus, is selected. Also, the conjugate of DOX and triphenylphosphonium (TPP‐DOX) is synthesized as sonosensitizer with mitochondrial targeting ability. DOX and TPP‐DOX are delivered to nucleus and mitochondria by nanocapsules. Furthermore, DOX‐ or TPP‐DOX‐loaded nanocapsules exhibit in vitro sonodynamic therapeutic effect to HeLa cells with sonication, which might be through oxidative damage to nucleus and mitochondria.

For the delivery of doxorubicin (DOX), pH and redox dual responsive hollow nanocapsules were prepared through the stabilization of polymer vesicles, which spontaneously formed from polyamidoamine dendron-poly(l-lysine) (PAMAM dendron-PLL), by the introduction of disulfide (SS) bonds between PLLs. The SS-bonded nanocapsules exhibited a very slow release of DOX under an extracellular environment because the cationic PLL membrane acted as an electrostatic barrier against the protonated DOX molecules. However, increasing the glutathione concentration to the intracellular level facilitated the immediate release of DOX through the collapse of nanocapsules by the spontaneous cleavage of SS bonds. SS-bonded nanocapsules also escaped from the endosome by the buffering effect of PAMAM dendrons, and DOX delivery into the cytoplasm was achieved. Furthermore, DOX molecules delivered by SS-bonded nanocapsules exhibited an effective in vitro anticancer effect to HeLa cells.