Polymeric micelles are promising carriers for anti-cancer agents due to their small size, ease of assembly, and versatility for functionalization. A current challenge in the use of polymeric micelles is the sensitive balance that must be achieved between stability during prolonged blood circulation and release of active drug at the tumor site. Stimuli-responsive materials provide a mechanism for triggered drug release in the acidic tumor and intracellular microenvironments. In this work, we synthesized a series of dual pH- and temperature-responsive block copolymers containing a poly(ε-caprolactone) (PCL) hydrophobic block with a poly(triethylene glycol) block that were copolymerized with an amino acid-functionalized monomer. The block copolymers formed micellar structures in aqueous solutions. An optimized polymer that was functionalized with 6-aminocaproic acid (ACA) possessed pH-sensitive phase transitions at mildly acidic pH and body temperature. Doxorubicin-loaded micelles formed from these polymers were stable at blood pH (~7.4) and showed increased drug release at acidic pH. In addition, these micelles displayed more potent anti-cancer activity than free doxorubicin when tested in a tumor xenograft model in mice.
1 February 2023 in Materials Science and Engineering: C
Chitosan has been investigated as a non-viral vector because it has several advantages such as biocompatibility, biodegradability and low toxicity with high cationic potential. However, the low specificity and low transfection efficiency of chitosan need to be solved prior to clinical application. In this paper, we focused on the galactose or mannose ligand modification of chitosan for enhancement of cell specificity and transfection efficiency via receptor-mediated endocytosis in vitro and in vivo.
Although the number of vascular surgeries using vascular grafts is increasing, they are limited by vascular graft-related complications and size discrepancy. Current efforts to develop the ideal synthetic vascular graft for clinical application using tissue engineering or 3D printing are far from satisfactory. Therefore, we aimed to re-design the vascular graft with modified materials and 3D printing techniques and also demonstrated the improved applications of our new vascular graft clinically. We designed the 3D printed polyvinyl alcohol (PVA) templates according to the vessel size and shape, and these were dip-coated with salt-suspended thermoplastic polyurethane (TPU). Next, the core template was removed to obtain a customized porous TPU graft. The mechanical testing and cytotoxicity studies of the new synthetic 3D templated vascular grafts (3DT) were more appropriate compared with commercially available polytetrafluoroethylene (PTFE) grafts (ePTFE; standard graft, SG) for clinical use. Finally, we performed implantation of the 3DTs and SGs into the rat abdominal aorta as a patch technique. Four groups of the animal model (SG_7 days, SG_30 days, 3DT_7 days, and 3DT_30 days) were enrolled in this study. The abdominal aorta was surgically opened and sutured with SG or 3DT with 8/0 Prolene. The degree of endothelial cell activation, neovascularization, thrombus formation, calcification, inflammatory infiltrates, and fibrosis were analyzed histopathologically. There was significantly decreased thrombogenesis in the group treated with the 3DT for 30 days compared with the group treated with the SG for 7 and 30 days, and the 3DT for 7 days. In addition, the group treated with the 3DT for 30 days may also have shown increased postoperative endothelialization in the early stages. In conclusion, this study suggests the possibility of using the 3DT as an SG substitute in vascular surgery.