Polymeric Gas Donor Micelles
Gaseous signal-transmitter molecules such as nitric oxide (NO), carbon monoxide (CO) and hydrogen sulfide (H2S) have the potential to act as therapeutic agents to treat pathological conditions like cancer and cardiovascular disease by regulating various signaling pathways. Toward the controlled delivery of these gaseous drugs, we are developing gas-releasing polymeric micelles, which are nanosized aggregates prepared from amphiphilic block copolymers, using controlled/living radical polymerization techniques and evaluating their biological activity in macrophages, endothelial cells and cancer cells.
T. Takatani-Nakase et al., Hydrogen Sulfide Donor Micelles Protect Cardiomyocytes from Ischemic Cell Death. Molecular BioSystems, 13 (2017) 1705-1708.
U. Hasegawa et al., Furoxan-Bearing Micelles for Nitric Oxide Delivery. Macromolecular Bioscience, 16 (2016) 1009-1018.
T. Wang et al., Nitric Oxide-Releasing Polymeric Furoxan Conjugates. Polymer Chemistry, 6 (2015) 7737– 7748.
U. Hasegawa et al., Polymeric Micelles for Hydrogen Sulfide Delivery. Medicinal Chemistry Communications, 6 (2015) 273-276.
U. Hasegawa et al., Design and Synthesis of Polymeric Hydrogen Sulfide Donors. Bioconjugate Chemistry, 25 (2014) 1290-1300.
U. Hasegawa et al., Carbon Monoxide-releasing Micelles for Immunotherapy. Journal of the American Chemical Society 132(51) (2010) 18273–18280.
Antioxidant Polymeric Micelles
Overproduction of reactive oxygen species (ROS), such as hydrogen peroxide (H2O2), superoxide anion (O2•-) and hydroxyl radical (OH•), induces tissue damage and inflammation, which is often associated with the initiation and progression of cancer and inflammatory diseases. Therefore, scavenging of endogenous ROS is of interest for treating these conditions. We are developing polymeric micelles with ROS scavenging moieties with long-lasting antioxidative activity and evaluating their anti-angiogenic and anti-cancer effects.
M. Moriyama et al., Inhibition of Angiogenesis by Antioxidant Micelles. Advanced Healthcare Materials, 4(4) (2015) 569-575.
U. Hasegawa et al., Antioxidant Micelles for Bortezomib Delivery. Colloid and Polymer Science, 293(7) (2015) 1887-1892.
U. Hasegawa et al., Catechol-Bearing Block Copolymer Micelles: Structural Characterization and Antioxidant Activity. Polymer, 66 (2015) 1-7.
M. Moriyama et al., Crosslinked Catechol-Bearing Poly(γ-Glutamic Acid) Self-Aggregates with Antioxidant Activity. Colloid and Polymer Science, 293(4) (2015) 1245-1251.
Phenylboronic Acid-bearing Framboidal Nanoparticles
Polymeric nanomaterials containing phenylboronic acid (PBA) groups have attracted considerable attention, especially in the field of biomedical engineering, due to their stimuli-responsiveness and chemical reactivity. We have developed a novel method to synthesize monodisperse PBA-containing polymeric nanoparticles with a unique framboidal morphology by aqueous dispersion polymerization. We are exploring the potential applications of these nanoparticles in drug delivery.
A. J. van der Vlies et al., Framboidal Nanoparticles Containing A Curcumin-Phenylboronic Acid Complex with Antiangiogenic and Anticancer Activities. Bioconjugate Chemistry, 30 (3) (2019) 861-870.
A. J. van der Vlies et al., Polymeric Framboidal Nanoparticles Loaded with a Carbon Monoxide Donor via Phenylboronic Acid-Catechol Complexation. Bioconjugate Chemistry, 27 (6) (2016) 1500-1508.
U. Hasegawa et al., Mannose-Displaying Fluorescent Framboidal Nanoparticles Containing Phenylboronic Acid Groups as a Potential Drug Carrier for Macrophage Targeting. Colloids and Surfaces B: Biointerfaces, 36 (2015) 1174-1181.
U. Hasegawa et al., Dual Stimuli-Responsive Phenylboronic Acid-Containing Framboidal Nanoparticles by One-Step Aqueous Dispersion Polymerization. Macromolecules, 48(13) (2015) 4388-4393.