HER-2-targeted boron neutron capture therapy using an antibody-conjugated boron nitride nanotube/ß-1,3-glucan complex.

The development of boron agents with integrated functionality, including biocompatibility, high boron content, and cancer cell targeting, is desired to exploit the therapeutic efficacy of boron neutron capture therapy (BNCT). Here, we report the therapeutic efficacy of BNCT using a HER-2-targeted antibody-conjugated boron nitride nanotube/ß-1,3-glucan complex. The anticancer effect of BNCT using our system was 30-fold that of the clinically available boron agent l-BPA/fructose complex.

Selective Photodynamic Activity of Tetrakis(4-aminophenyl)porphyrins with and without Acetyl Protecting Groups on Cancer and Normal Cells.

Tetrakis(4-aminophenyl)porphyrin (1) and tetrakis(4-acetamidophenyl)porphyrin (2) were dissolved in water with the incorporation of a polysaccharide (λ-carrageenan (CGN)) as a water-solubilizing agent. Although the photodynamic activity of the CGN-2 complex was considerably lower than that of the CGN-1 complex, the selectivity index (SI; IC50 in a normal cell/IC50 in a cancer cell) of the CGN-2 complex was considerably higher than that of the CGN-1 complex. This is because the photodynamic activity of the CGN-2 complex was significantly affected by the intracellular uptakes by the normal and cancer cells. During in vivo experiments, the CGN-2 complex inhibited tumor growth under light irradiation with high blood retention compared with the CGN-1 complex and Photofrin, which exhibited lower blood retention. This study showed that the photodynamic activity and SI are influenced by substituent groups of arene in the meso-positions of porphyrin analogs.

Controlled Release of Drug-Encapsulated Protein Films with Various Sodium Dodecyl Sulfate Concentrations.

Protein-based drug carriers are ideal drug-delivery platforms because of their biocompatibility, biodegradability, and low toxicity. Many types and shapes of protein-based platforms, including nanoparticles, hydrogels, films, and minipellets, have been prepared to deliver drug molecules. In this study, protein films containing the desired amounts of doxorubicin (DOX) as cancer drugs were developed using a simple mixing method. The release ratio and rate of DOXs were dependent on the surfactant concentration. The drug release ratio was controlled within the range of 20-90% depending on the amount of the surfactant used. The protein film surface was analyzed using a microscope before and after drug release, and the relationship between the degree of film swelling and the drug release ratio was discussed. Moreover, the effects of cationic surfactants on the protein film were investigated. Non-toxic conditions of the protein films were confirmed in normal cells, while the toxicity of the drug-encapsulated protein film was confirmed in cancer cells. Remarkably, it was observed that the drug-encapsulated protein film could eliminate 10-70% of cancer cells, with the extent of efficacy varying based on the surfactant amount.

Carborane bearing pullulan nanogel-boron oxide nanoparticle hybrid for boron neutron capture therapy.

Boron neutron capture therapy shows is a promising approach to cancer therapy, but the delivery of effective boron agents is challenging. To address the requirements for efficient boron delivery, we used a hybrid nanoparticle comprising a carborane = bearing pullulan nanogel and hydrophobized boron oxide nanoparticle (HBNGs) enabling the preparation of highly concentrated boron agents for efficient delivery. The HBNGs showed better anti-cancer effects on Colon26 cells than a clinically boron agent, L-BPA/fructose complex, by enhancing the accumulation and retention amount of the boron agent within cells in vitro. The accumulation of HBNGs in tumors, due to the enhanced permeation and retention effect, enabled the delivery of boron agents with high tumor selectivity, meeting clinical demands. Intravenous injection of boron neutron capture therapy (BNCT) using HBNGs decreased tumor volume without significant body weight loss, and no regrowth of tumor was observed three months after complete regression. The therapeutic efficacy of HBNGs was better than that of L-BPA/fructose complex. BNCT with HBNGs is a promising approach to cancer therapeutics.

Development of a Water-Dispersible Supramolecular Complex of Polyphenol with Polypeptides for Attenuation of the Allergic Response using a Mechanochemical Strategy.

The prevalence of allergic disorders has increased worldwide in recent decades. Polyphenols, including resveratrol and curcumin, are posited to have potential as therapeutic agents for allergy; however, their use has been limited by poor water solubility. Accordingly, a highly concentrated, water dispersible, supramolecular complexes of polyphenols with polypeptides (poly-L-lysine, poly-γ-glutamic acid) and gelatin using high-speed vibration milling are developed. The complex exhibits resistance to photobleaching and thermal radiation. Treatment of a rat basophilic leukemia cell line (RBL-2H3) with polypeptide complexes containing resveratrol is suppressed allergic responses in vitro. Moreover, aerosolized administration of polypeptide complexes demonstrates excellent bioavailability and inhibition of immediate hypersensitivity reactions in ear tissue in vivo. Furthermore, the method avoids the use of organic solvent and therefore reduces undesirable biological responses.

Drug-Loaded Biocompatible Chitosan Polymeric Films with Both Stretchability and Controlled Release for Drug Delivery.

Chitosan is a natural polysaccharide with the advantageous qualities of biocompatibility and biodegradability, and it has recently been spotlighted as a soft material for a sustainable society. Advantages such as these are in demand for application in various biomaterials. Although extensive studies have been conducted on the preparation of chitosan films, overcoming the problems of weak mechanical properties remains a significant barrier. In the present study, we developed stretchable doxorubicin-loaded biocompatible chitosan films by adding acetic acid in controlled concentrations. The stretchable properties of doxorubicin-loaded chitosan film at various concentrations of acetic acid were measured. Elongation to the point of breakage reached 27% with a high concentration of acetic acid, which could be described as high stretchability. The release ratio of doxorubicin from chitosan film reached 70% with a high acetic acid concentration. The cytotoxicity of doxorubicin-loaded chitosan films was measured, and cancer spheroids had completely collapsed after 7 days. According to the results of skin permeability testing, use of the doxorubicin-loaded chitosan film is a plausible choice for a drug sealant.

Formulation of water-dispersible hydrophobic compound nanocomplexes with polypeptides via a supramolecular approach using a high-speed vibration milling technique.

Polypeptides were used to solubilize functional hydrophobic molecules via a high-speed vibrational milling method. Poly-l-lysine and poly-γ-glutamic acid, which are polypeptides, were able to prepare more highly concentrated water-dispersible complexes of hydrophobic compounds, including fullerenes, organic dyes, and porphyrin derivatives, than conventional water solubilizers, such as cyclodextrins and pullulan. In addition, the polypeptide systems endowed the complexes with long-term stability and resistance against thermal stress, which is advantageous for industrial applications. Furthermore, complexes of polypeptides and porphyrin derivatives showed a photodynamic activity against cancer cells, and the current system improved the dispersibility and storability of guest molecules without compromising their functionality.

Theranostic Agent Combining Fullerene Nanocrystals and Gold Nanoparticles for Photoacoustic Imaging and Photothermal Therapy.

Developing photoactivatable theranostic platforms with integrated functionalities of biocompatibility, targeting, imaging contrast, and therapy is a promising approach for cancer diagnosis and therapy. Here, we report a theranostic agent based on a hybrid nanoparticle comprising fullerene nanocrystals and gold nanoparticles (FGNPs) for photoacoustic imaging and photothermal therapy. Compared to gold nanoparticles and fullerene crystals, FGNPs exhibited stronger photoacoustic signals and photothermal heating characteristics by irradiating light with an optimal wavelength. Our studies demonstrated that FGNPs could kill cancer cells due to their photothermal heating characteristics in vitro. Moreover, FGNPs that are accumulated in tumor tissue via the enhanced permeation and retention effect can visualize tumor tissue due to their photoacoustic signal in tumor xenograft model mice. The theranostic agent with FGNPs shows promise for cancer therapy.