Asthma is an intractable disease involving the infiltration of inflammatory cells and mucus plugging. Despite small molecular mucolytics having the ability to break the disulfide bonds of mucins, offering a potential way to overcome the airflow obstruction and airway infection, these mucolytics have limited therapeutic effects in vivo. Therefore, in this work, arginine-grafted chitosan (CS-Arg) is ionically cross-linked with tris(2-carboxyethyl)phosphine (TCEP) to obtain nanogels as a mucolytic agent. The positively charged nanogels effectively inhibit the formation of large aggregates of mucin in vitro, probably thanks to the formation of an ionic interaction between CS-Arg and mucin, as well as the breakage of disulfide bonds in mucin by the reductive TCEP. Moreover, the nanogels show good cytocompatibility at concentrations up to 5 mg mL −1 , exhibiting effective inhibitory effects against the proliferation of both Staphylococcus aureus and Escherichia coli at 5 mg mL −1 . After the administration of the nanogels by nebulization into a Balb/c mouse model with allergic asthma, they can efficiently reduce the mucus obstruction in bronchioles and alveoli and relieve airway inflammation. Therefore, these CS-Arg/TCEP nanogels potentially represent a promising mucolytic agent for the efficient treatment of allergic asthma and other muco-obstructive diseases.
Objective: Titanium dioxide nanoparticles (TiO 2) nanoparticles have been widely explored in the prevention of cancer risk. Due to the difficult solubility of TiO 2 nanoparticles, it is essential to synthesize new surfactants to increase its bioavailability and anti-tumor activity and reduce its cytotoxicity. Furthermore, oxidative and inflammation are closely associated with the osteosarcoma risk. Chitosan has biocompatibility, antioxidant and anti-inflammatory properties. The effects of chitosan-coated TiO 2-embedded paclitaxel nanoparticles on an osteosarcoma model were explored. Methods: An osteosarcoma model was established and chitosan-coated TiO 2embedded paclitaxel nanoparticles were prepared using a freeze-drying strategy. The morphological characteristics of nanoparticles were observed using scanning electron microscopy (SEM). The physicochemical properties of nanoparticle were evaluated by X-ray diffraction (XRD) and Fourier transform infrared (FTIR) spectroscopy. The cytotoxicity was tested by using human osteoblast cells hFob1.19 and osteosarcoma cells 143B. Osteosarcoma mice were treated with PBS buffer, paclitaxel, TiO 2embedded paclitaxel and chitosan-coated TiO 2-embedded paclitaxel nanoparticles. The biomarkers of oxidative-inflammatory status, anti-tumor activities and survival rates of the model were measured. Results: XRD analysis showed that the peaks of chitosan/TiO 2 (anatase) were consistent with those of crystalline TiO 2 and broad phase of chitosan. The FTIR spectrum indicated the relevant functional groups in TiO 2. Chitosan-coated TiO 2embedded paclitaxel nanoparticles had good biocompatibility and improve antioxidant and anti-inflammatory properties in the osteosarcoma model. Chitosan-coated TiO 2embedded paclitaxel nanoparticles was less toxic to the cells hFob1.19 and more toxic to the cells 143B than TiO 2-embedded paclitaxel nanoparticles. Chitosan-coated TiO 2embedded paclitaxel nanoparticles showed significant antitumor activity and increased the survival rate of the osteosarcoma model (P < 0.05). Conclusions: Chitosan improved anti-tumor potential of TiO 2-embedded paclitaxel nanoparticles in the prevention of osteosarcoma.
The fusion of protein science and peptide science opens up new frontiers in creating innovative biomaterials. Herein, a new kind of adhesive soft materials based on a natural occurring plant protein and short peptides via a simple co‐assembly route are explored. The hydrophobic zein is supercharged by sodium dodecyl sulfate to form a stable protein colloid, which is intended to interact with charge‐complementary short peptides via multivalent ionic and hydrogen bonds, forming adhesive materials at macroscopic level. The adhesion performance of the resulting soft materials can be fine‐manipulated by customizing the peptide sequences. The adhesive materials can resist over 78 cmH2O of bursting pressure, which is high enough to meet the sealing requirements of dural defect. Dural sealing and repairing capability of the protein‐peptide biomaterials are further identified in rat and rabbit models. In vitro and in vivo assays demonstrate that the protein‐peptide adhesive shows excellent anti‐swelling property, low cell cytotoxicity, hemocompatibility, and inflammation response. In particular, the protein‐peptide supramolecular biomaterials can in vivo dissociate and degrade within two weeks, which can well match with the time‐window of the dural repairing. This work underscores the versatility and availability of the supramolecular toolbox in the easy‐to‐implement fabrication of protein‐peptide biomaterials.
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