Lumazine Synthase Protein Nanoparticle-Gd(III)-DOTA Conjugate as a T1 contrast agent for high-field MRI.

With the applications of magnetic resonance imaging (MRI) at higher magnetic fields increasing, there is demand for MRI contrast agents with improved relaxivity at higher magnetic fields. Macromolecule-based contrast agents, such as protein-based ones, are known to yield significantly higher r1 relaxivity at low fields, but tend to lose this merit when used as T1 contrast agents (r1/r2 = 0.5 ~ 1), with their r1 decreasing and r2 increasing as magnetic field strength increases.

Polyvalent display of monosaccharides on ferritin protein cage nanoparticles for the recognition and binding of cell-surface lectins.

Carbohydrate-lectin interactions are important in many biological events. Endogenous cell-surface lectins are attractive markers for the recognition and targeting. Human ferritin protein cage nanoparticles (HFPCNs) are prepared as delivery nanoplatforms and two different types of monosaccharide derivatives; maleimido group terminated-mannopyranoside and galactopyranoside.

Ferritin protein cage nanoparticles as versatile antigen delivery nanoplatforms for dendritic cell (DC)-based vaccine development.

Unlabelled: We utilized ferritin protein cage nanoparticles (FPCN) as antigen delivery nanoplatforms for DC-based vaccine development and investigated DC-mediated antigen-specific immune responses. Antigenic peptides, OT-1 (SIINFEKL) or OT-2 (ISQAVHAAHAEINEAGR) which are derived from ovalbumin, were genetically introduced either onto the exterior surface or into the interior cavity of FPCN. FPCN carrying antigenic peptides (OT-1-FPCN and OT-2-FPCN) were effectively delivered to DCs and processed within endosomes.

Fabrication of uniform layer-by-layer assemblies with complementary protein cage nanobuilding blocks via simple His-tag/metal recognition.

A capsid-forming enzyme, lumazine synthase isolated from hyperthermophile Aquifex aeolicus (AaLS), is prepared and utilized as a template for constructing nanobuilding blocks to fabricate uniform layer-by-layer (LbL) assemblies. Two functionally complementary AaLS protein cage nanoparticles (PCNs) are generated either by genetically introducing His-tags on the surface of wild-type AaLS PCNs or by chemically attaching metal chelates (Ni-NTA moiety) to the surface of cysteine-bearing AaLS PCNs individually. The multivalent displays of His-tags (AaLS-His PCN) and Ni-NTA ligands (AaLS-NTA-Ni PCN) on the surface of each complementary AaLS PCN are successfully demonstrated by mass spectrometric and surface plasmon resonance analyses.

Natural polypeptide-based supramolecular nanogels for stable noncovalent encapsulation.

Supramolecular nanogel, a physically cross-linked nanosize hydrogel, spontaneously self-assembles in aqueous solution via secondary interactions and is thus of great interest in nanomedicine as a drug carrier. We developed a versatile method for supramolecular nanogel self-assembled by electrostatic interaction between positive surfactant micelles and negative polypeptides. Core-shell-like structures of supramolecular nanogels provide stable hydrophobic pockets that prevent simple diffusion of hydrophobic guest molecules, resulting in high encapsulation stability.

Incorporation of thrombin cleavage peptide into a protein cage for constructing a protease-responsive multifunctional delivery nanoplatform.

Protein cages are spherical hollow supramolecules that are attractive nanoscale platforms for constructing cargo delivery vehicles. Using ferritin isolated from the hyperthermophilic archaeon Pyrococcus furiosus (Pf_Fn), we developed a multifunctional protein cage-based delivery nanoplatform that can hold cargo molecules securely, deliver them to the targeted sites, and release them to the targeted cells. The release is triggered by cleavage induced by the protease, thrombin.

Glucose-Responsive Disassembly of Polymersomes of Sequence-Specific Boroxole-Containing Block Copolymers under Physiologically Relevant Conditions.

Polymers containing organoboronic acids have recently gained interest as sugar-responsive materials owing to the reversible binding of saccharides to boronic acids, which triggers a change in the physical and chemical properties of these polymers, such as their water solubility. In particular, the ability of these polymers to bind glucose has attracted considerable attention because of the promise of these materials for the development of sensors and drug delivery systems for glucose-related human diseases, such as diabetes. We report here a new class of sugar-responsive polymers that are based on a sequence-specific copolymer of styreneboroxole and -functionalized maleimide.

Development of protein-cage-based delivery nanoplatforms by polyvalently displaying β-cyclodextrins on the surface of ferritins through copper(I)-catalyzed azide/alkyne cycloaddition.

Protein cages are spherical hollow macromolecules that are attractive platforms for the construction of nanoscale cargo delivery vehicles. Human heavy-chain ferritin (HHFn) is modified genetically to control the number and position of functional groups per cage. 24 β-CDs are conjugated precisely to the modified HHFn in specific locations through thiol-maleimide Michael-type addition followed by copper(I)-catalyzed azide/alkyne cycloaddition (CuAAC).

Developing an antibody-binding protein cage as a molecular recognition drug modular nanoplatform.

We genetically introduced the Fc-binding peptide (FcBP) into the loop of a self-assembled protein cage, ferritin, constituting four-fold symmetry at the surface to use it as a modular delivery nanoplatform. FcBP-presenting ferritin (FcBP-ferritin) formed very stable non-covalent complexes with both human and rabbit IgGs through the simple molecular recognition between the Fc region of the antibodies and the Fc-binding peptide clusters inserted onto the surface of FcBP-ferritin. This approach realized orientation-controlled display of antibodies on the surfaces of the protein cages simply by mixing without any complicated chemical conjugation.

Monosaccharide-responsive release of insulin from polymersomes of polyboroxole block copolymers at neutral pH.

We synthesized a boroxole-containing styrenic monomer that can be polymerized by the reversible addition-fragmentation and chain transfer (RAFT) method. Poly(styreneboroxole) (PBOx) and its block copolymers with a poly(ethylene glycol) (PEG) as a hydrophilic block displayed binding to monosaccharides in phosphate buffer at neutral pH, as quantified by Wang's competitive binding experiments. By virtue of a controlled radical polymerization, we were able to adjust the degree of polymerization of the PBOx block to yield sugar-responsive block copolymers that self-assembled into a variety of nanostructures including spherical and cylindrical micelles and polymer vesicles (polymersomes).

Molecular interaction between HAX-1 and XIAP inhibits apoptosis.

Caspase-3 is an important executor caspase that plays an essential role in apoptosis. Recently, HS1-associated protein X1 (HAX-1) was found to be a substrate of caspase-3. Although HAX-1 has serve multifunctional roles in cellular functions such as cell survival and calcium homeostasis, the detailed functional mechanism of HAX-1 remains still unclear.