Murakami group is aiming at developing novel cell engineering technologies for therapy and drug delivery systems against intractable diseases by external stimuli-responsive nanomaterials. In both cases, how the nanomaterials are delivered to a specific site of interest is one of the most important challenges. This is because their output, e.g., heat, can be cytotoxic and cause adverse effects on our body unless spatially controlled. Furthermore, such nanomaterials themselves must be stable under physiological conditions and biocompatible. We are trying to overcome these challenges with naturally occurring nanomaterials in our body for biocompatible carriers / dispersants. In particular, the biocompatible nanomaterials are genetically and chemically engineered so that external stimuli-responsive nanomaterials are easily incorporated into them and targeted to a specific site in vitro and in vivo.
The followings are ongoing cross-disciplinary research projects in collaboration with several domestic and international (ETH) labs.
- 1. Development of surface biocompatibilization and functionalization technologies for external stimuli-responsive nanomaterials
- 2. Precise localization of photoreactive nanomaterials in cells and photoregulation of cell functions
- 3. Precise localization of photreactive nanomaterials in our body and phototherapy against intractable diseases
- 4. Development of in vivo gene carrier systems with naturally occurring nanomaterials
1. Electron microscopy images of photoresponsive nanomaterials that our group focuses on.
(a) Gold nanorod (left) and carbon nanotubes (right).
(b) Photographs of aqueous dispersions of semiconducting- (left) and metallic- (right) enriched carbon nanotubes.
Gold nanorods adsorb near-infrared light to emit heat with high efficiency. Carbon nanotubes can also do that, and semiconducting-enriched ones generate reactive oxygen species as well upon near-infrared irradiation. Our group found that reactive oxygen species from the irradiated carbon nanotubes can kill cancer cells.
2. Schematic illustration of naturally occurring nanomaterial and its various functionalizations.
High-density lipoprotein (HDL) is believed to have a discoidal phospholipid circumscribed with a few lipid-binding proteins (apoA-I). HDL has been functionalized in various ways as follows: chemical modification of the apoA-I moiety, membrane charge control with charged lipids, membrane anchoring of functional molecules via hydrophobic moieties, genetic engineering of apoA-I for functional peptide/protein fusion, size control by hydrophobic drug loading. Our group found that cell-penetrating HDL can be developed through genetic fusion of a cell-penetrating peptide with apoA-I and that upon preparation with increased amount of phospholipids, HDL can efficiently incorporate hydrophobic drugs and interestingly be enlarged in a manner dependent on the amount of the drug incorporated.
3. Electron microscopy image of cell-penetrating HDL mutants sticking on outer plasma membrane (a) and its schematic illustration (b).
The mutants in grey formed clusters (arrows) just within 2 min after the addition. After a short period, they are internalized. One of our research goals is to elucidate how the HDL mutants interact with and are internalized by cells. This study will provide important insight into the development of gene delivery systems. This photograph was taken by Dr. Morone in Heuser Lab .
↑ Its schematic illustration （b）
← Electron microscopy image (a)