Extracellular deposition of β-amyloid (Aβ) peptide aggregates is a major characteristic of Alzheimer’s disease (AD) brain. Because Aβ peptide aggregates aggravate neuropathy and cognitive impairment for AD patients, numerous efforts have been devoted to suppressing Aβ self-assembly as a prospective AD treatment option. Here, we report Aβ-targeting, red-light-responsive carbon dots (CDs), and their therapeutic functions as a light-powered nanomodulator to spatiotemporally suppress toxic Aβ aggregation both in vitro and in vivo. Our aptamer-functionalized carbon dots (Apta@CDs) showed strong targeting ability toward Aβ42 species. Moreover, red LED irradiation induced Apta@CDs to irreversibly denature Aβ peptides, impeding the formation of β-sheet-rich Aβ aggregates and attenuating Aβ-associated cytotoxicity. Consequently, Apta@CDs-mediated photomodualtion modality achieved effective suppression of Aβ aggregation in vivo, which significantly reduced the Aβ burden at the targeted sites in the brain of 5xFAD mice by ∼40% and ∼25% according to imaging and ELISA analyses, respectively. Our work demonstrates the therapeutic potential of photomodulating CDs for light-driven suppression against Aβ self-assembly and related neurotoxicity.
Bone contains an organic matrix composed of aligned collagen fibers embedded with nanosized inorganic hydroxyapatite (HAp). Many efforts are being made to mimic the natural mineralization process and create artificial bone scaffolds that show elaborate morphologies, excellent mechanical properties, and vital biological functions. This study reports a newly discovered function of lignin mediating the formation of human bone-like HAp. Lignin is the second most abundant organic material in nature, and it exhibits many attractive properties for medical applications, such as high durability, stability, antioxidant and antibacterial activities, and biocompatibility. Numerous phenolic and aliphatic hydroxyl moieties exist in the side chains of lignin, which donate adequate reactive sites for chelation with Ca 2+ and the subsequent nucleation of HAp through coprecipitation of Ca 2+ and PO 4 3− . The growth of HAp crystals was facilitated by simple incubation of the electrospun lignin/polycaprolactone (PCL) matrix in a simulated body fluid. Multiple analyses revealed that HAp crystals were structurally and mechanically similar to the native bone. Furthermore, the mineralized lignin/PCL nanofibrous films facilitated efficient adhesion and proliferation of osteoblasts by directing filopodial extension. Our results underpin the expectations for this ligninbased biomaterial in future biointerfaces and hard-tissue engineering.
Hydrogels possess favorable physical properties ideally suited for various biotechnology applications. To tailor to specific needs, a number of modification strategies have been employed to tune their properties. Herein, a multifunctional polymeric cross-linker based on polyaspartamide is developed, which allows for the facile adjustment of the type and number of reactive functional groups to fit different reaction schemes and control the physical properties of the hydrogels. The amine-based nucleophiles containing desired functional groups are reacted with polysuccinimide to synthesize polyaspartamide cross-linkers. The cross-linking density and the concurrent change in mechanical properties of the resulting hydrogels are controlled in a wide range only with the degree of substitution. This multivalency of the polyaspartamide linkers also induced the degradation of hydrogels by the unreacted functional groups on polyaspartamide involved in the hydrolysis. Furthermore, the polyaspartamide cross-linker conjugated with cell-recognition molecules via the same conjugation mechanism (i.e., nucleophilic substitution) render the hydrogels cell-responsive without the need of additional processing steps. This versatility of polyaspartamide-based cross-linker is expected to provide an efficient and versatile route to engineer hydrogels with controllable properties for biomedical applications.
Organic–inorganic hybrid perovskite nanoparticles (NPs) are a very strong candidate emitter that can meet the high luminescence efficiency and high color standard of Rec.2020. However, the instability of perovskite NPs is the most critical unsolved problem that limits their practical application. Here, an extremely stable crosslinked perovskite NP (CPN) is reported that maintains high photoluminescence quantum yield for 1.5 years (>600 d) in air and in harsher liquid environments (e.g., in water, acid, or base solutions, and in various polar solvents), and for more than 100 d under 85 °C and 85% relative humidity without additional encapsulation. Unsaturated hydrocarbons in both the acid and base ligands of NPs are chemically crosslinked with a methacrylate‐functionalized matrix, which prevents decomposition of the perovskite crystals. Counterintuitively, water vapor permeating through the crosslinked matrix chemically passivates surface defects in the NPs and reduces nonradiative recombination. Green‐emitting and white‐emitting flexible large‐area displays are demonstrated, which are stable for >400 d in air and in water. The high stability of the CPN in water enables biocompatible cell proliferation which is usually impossible when toxic Pb elements are present. The stable materials design strategies provide a breakthrough toward commercialization of perovskite NPs in displays and bio‐related applications.
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