Advanced Drug Delivery Modulation via Hybrid Nanofibers Enhances Stem Cell Differentiation.

Seamlessly integrating soluble factors onto biomedical scaffolds with a precisely manufactured topography for efficient cell control remains elusive since many scaffold fabrication techniques degrade payloads. Surface adsorption of payloads onto synthesized nanoscaffolds retains bioactivity by removing exposure to harsh processing conditions at the expense of inefficient drug loading and uncontrolled release. Herein, we present a nanomaterial composite scaffold paradigm to improve physicochemical surface adsorption pharmacokinetics. As a proof of concept, we integrated graphene oxide (GO) and manganese dioxide (MnO2) nanosheets onto nanofibers to increase loading capacity and tune drug release. Non-degradable GO enhances payload retention, while biodegradable MnO2 enables cell-responsive drug release. To demonstrate the utility of this hybrid nanomaterial scaffold paradigm for tissue engineering, we adsorbed payloads ranging from small molecules to proteins onto the scaffold to induce myogenesis and osteogenesis for multiple stem cell lines. Scaffolds with adsorbed payloads enabled more efficient differentiation than media supplementation using equivalent quantities of differentiation factors. We attribute this increased efficacy to a reverse uptake mechanism whereby payloads are localized around seeded cells, increasing delivery efficiency for guiding differentiation. Additionally, we demonstrate spatial control over cells since differentiation factors are delivered locally through the scaffold. When co-culturing scaffolds with and without adsorbed payloads, only cells seeded on payload-adsorbed scaffolds underwent differentiation. With this modular technology being capable of enhancing multiple differentiation fates for specific cell lines, this technology provides a promising alternative for current tissue engineering scaffolds.

Programmed degradation of a hierarchical nanoparticle with redox and light responsivity for self-activated photo-chemical enhanced chemodynamic therapy.

Chemodynamic therapy (CDT) has recently emerged as a promising treatment for cancer due to the high specificity of CDT towards tumor microenvironment (TME). However, the low efficiency of reactive oxygen species (ROS) generation and the robust ROS defensive mechanisms in cancer cells remain critical hurdles for current CDT. Addressing both challenges in a single platform, we developed a novel redox and light-responsive (RLR) nanoparticle with a core-shell structure. Remarkably, our hierarchical RLR nanoparticle is composed of an ultrasmall Fe3O4 nanoparticle engineered framework of hollow carbon matrix core and a nanoflower-like MnO2 shell. Under the abundant overexpressed glutathione (GSH) and acidic nature in TME, the RLR nanoparticle was programmed to degrade and self-activate CDT-induced cancer-killing by accelerating ROS generation via overcoming the ROS defensive mechanisms based on the depletion of intracellular GSH, the sequential production of theranostic ion species (e.g., Mn2+ and Fe2+), a spatiotemporal controllable photothermal hyperthermia and a redox triggered chemotherapeutic drug release. Additionally, the carbon framework of RLR nanoparticle could collapse by leaching of iron ions. An excellent selective and near-complete tumor suppression based on the RLR nanoparticles through a strong synergy between CDT, PTT and anti-cancer drugs was demonstrated via in vitro and in vivo anti-tumoral assays.