ABSTRACT
Glioblastoma (GBM) is a central nervous system cancer with high incidence and poor survival rates. Enhancing drug penetration of the blood-brain barrier (BBB) and targeting efficacy is crucial for improving treatment outcomes. In this study, we developed a redox-sensitive targeted nano-delivery system (HCA-A2) for temozolomide (TMZ) and ß-lapachone (ß-Lapa). This system used hyaluronic acid (HA) as the hydrophilic group, arachidonic acid (CA) as the hydrophobic group, and angiopep-2 (A2) as the targeting group. Control systems included non-redox sensitive (HDA-A2) and non-targeting (HCA) versions. In vitro, HCA-TMZ-Lapa micelles released 100 % of their payload in a simulated tumor microenvironment within 24 h, compared to 43.97 % under normal conditions. HCA-A2 micelles, internalized via clathrin-mediated endocytosis, showed stronger cytotoxicity and better BBB penetration and cellular uptake than controls. In vivo studies demonstrated superior tumor growth inhibition with HCA-A2 micelles, indicating their potential for GBM treatment.
Subject(s)
Blood-Brain Barrier , Brain Neoplasms , Glioblastoma , Micelles , Naphthoquinones , Oxidation-Reduction , Temozolomide , Glioblastoma/drug therapy , Glioblastoma/metabolism , Glioblastoma/pathology , Humans , Animals , Temozolomide/pharmacology , Temozolomide/chemistry , Temozolomide/administration & dosage , Naphthoquinones/chemistry , Naphthoquinones/pharmacology , Naphthoquinones/administration & dosage , Mice , Brain Neoplasms/drug therapy , Brain Neoplasms/metabolism , Brain Neoplasms/pathology , Blood-Brain Barrier/metabolism , Blood-Brain Barrier/drug effects , Drug Delivery Systems , Cell Line, Tumor , Mice, Nude , Hyaluronic Acid/chemistry , Peptides/chemistry , Peptides/pharmacologyABSTRACT
Uncontrolled hemorrhage of deep, narrow, and non-compressible perforating wounds is responsible for many trauma deaths. In this study, a rapid hemostatic sponge with an orderly channel based on methacrylated collagen (ColMA) was prepared via directional freeze-drying technology. The methacrylated hyaluronate (HAMA) was added to further enhance the mechanical properties of the sponge. The sponge presents excellent mechanical strength, rapid shape recovery, and absorption speed, which was faster than those of many reported natural polymer hemostatic sponges. Moreover, ColMA/HAMA sponge showed much better blood-clotting capacity and superior hemostasis performance than commercially available collagen sponges in vitro and in the rat-liver injury model. This study demonstrated a feasible strategy to construct the rapid hemostatic sponge with an orderly channel for the deep and non-compressible perforating wound.