Iodine-Rich Semiconducting Polymer Nanoparticles for CT/Fluorescence Dual-Modal Imaging-Guided Enhanced Photodynamic Therapy.

Photodynamic therapy (PDT) is a promising technique for cancer therapy, providing good therapeutic efficacy with minimized side effect. However, the lack of oxygen supply in the hypoxic tumor site obviously restricts the generation of singlet oxygen (1 O2 ), thus limiting the efficacy of PDT. So far, the strategies to improve PDT efficacy usually rely on complicated nanosystems, which require sophisticated design or complex synthetic procedure. Herein, iodine-rich semiconducting polymer nanoparticles (SPN-I) for enhanced PDT, using iodine-induced intermolecular heavy-atom effect to elevate the 1 O2 generation, are designed and prepared. The nanoparticles are composed of a near-infrared (NIR) absorbing semiconducting polymer (PCPDTBT) serving as the photosensitizer and source of fluorescence signal, and an iodine-grafted amphiphilic diblock copolymer (PEG-PHEMA-I) serving as the 1 O2 generation enhancer and nanocarrier. Compared with SPN composed of PEG-b-PPG-b-PEG and PCPDTBT (SPN-P), SPN-I can enhance the 1 O2 generation by 1.5-fold. In addition, SPN-I have high X-ray attenuation coefficient because of the high density of iodine in PEG-PHEMA-I, providing SPN-I the ability of use with computed tomography (CT) and fluorescence dual-modal imaging. The study thus provides a simple nanotheranostic platform composed of two components for efficient CT/fluorescence dual-modal imaging-guided enhanced PDT.

Superelastic and superflexible cellulose aerogels for thermal insulation and oil/water separation.

Aerogels with low thermal conductivity and high adsorption capacity present a promising solution to curb water pollution caused by organic reagents as well as mitigate heat loss. Although aerogels exhibiting good adsorption capacity and thermal insulation have been reported, materials with mechanical integrity, high flexibility and shear resistance still pose a formidable task. Here, we produced bacterial cellulose-based ultralight multifunctional hybrid aerogels by using freeze-drying followed by chemical vapor deposition silylation method. The hybrid aerogels displayed a low density of 10-15 mg/cm3, high porosity exceeding 99.1 %, low thermal conductivity (27.3-29.2 mW/m.K) and superior hydrophobicity (water contact angle>120o). They also exhibited excellent mechanical properties including superelasticity, high flexibility and shear resistance. The hybrid aerogels demonstrated high heat shielding efficiency when used as an insulating material. As a selective oil absorbent, the hybrid aerogels exhibit a maximum adsorption capacity of up to approximately 156 times its own weight and excellent recoverability. Especially, the aerogel's highly accessible porous microstructure results in an impressive flux rate of up to 162 L/h.g when used as a filter in a continuous oil-water separator to isolate n-hexane-water mixtures. This work presents a novel endeavor to create high-performance, sustainable, reusable, and adaptable multifunctional aerogels.

Local delivery of gambogic acid to improve anti-tumor immunity against oral squamous cell carcinoma.

Oral squamous cell carcinoma (OSCC) accounts for nearly 90% of oral cavity malignancies. However, despite significant advances in the last four decades, little improvement has been achieved in the overall survival rates for OSCC patients. While gambogic acid (GA) is a potential candidate compound for treating a variety of malignancies, its anti-cancer impact on OSCC has not to be completely investigated. The tumor immune microenvironment (TIME) has been proven to play a crucial role in the prognosis of cancer patients. Although there are few reports on the T cell activation effect of GA, the regulation of GA on the TIME of OSCC has barely been studied yet. In this study, GA was applied to treat OSCC-bearing mice through in situ controlled release. First, GA-loaded mPEG2000-PCL micelles (GA-MIC) were prepared by the thin-film hydration method to improve the aqueous dispersibility of GA. Second, poly(D, l-lactide)-poly(ethylene glycol)-poly(D, l-lactide) (PLEL) was synthesized for thermosensitive hydrogel preparation. Third, GA-MIC was mixed with PLEL to form an injectable therapeutic hydrogel (GA-MIC-GEL). The anti-tumor and TIME regulation effects of GA-MIC-GEL on tumor-bearing mice were further examined. The results showed that the thermosensitive GA-MIC-GEL with sensitive sol-gel transition characteristics could form hydrogel at 37 °C within 24 s, facilitating the local delivery and sustained GA release. Biochemical, hematological, and pathological analysis proved that GA-MIC-GEL has good biological safety. Moreover, GA-MIC-GEL promoted an obvious regression of both primary and distant tumors on the OSCC mouse models. Mechanically, GA-MIC-GEL down-regulated the expression of PD-1, increased the frequency of cytotoxic T cells and reduced the immunosuppressive cellular components, which boosted the anti-tumor immunity of OSCC-bearing mice. The constructed thermosensitive hydrogel for local delivery of GA has provided a safe and effective strategy with great potential for OSCC therapy.

Highly mechanical properties nanocomposite hydrogels with biorenewable lignin nanoparticles.

Biorenewable polymers from natural resources have attracted a greater attention of the research for different applications. In this work, renewable lignin nanoparticles (LNP) were employed as cross-linking junctions to prepare high mechanical properties hydrogel, polyacrylamide/lignin nanoparticle (PAM/LNP) nanocomposite hydrogel. The hydrogel exhibits high compressive and tensile strengths as well as excellent recoverability. The fracture strength of the PAM/LNP hydrogel under compressive stress is on the order of megapascals, which is several orders of magnitude higher than those of pure PAM hydrogel. The synergic improving effect of nanocomposite network structure and the strong H-bonding between polymer chains endow the hydrogel with an excellent mechanism of distributing the applied load. Considering good mechanical properties, simple synthesis methods and noncytotoxicity, this high performance hydrogel material has potential applications in biomedical fields, such as tissue engineering or regeneration, artificial muscles, strong underwater antifouling materials, and so on.

Grading and quantification of dental fluorosis in zebrafish larva.

OBJECTIVE: The prevalence and severity of dental fluorosis in primary teeth are different from permanent teeth. Previous animal models of dental fluorosis mainly focus on juvenile rats, mice and zebrafish. Our experiment aims to set a dental fluorosis model using zebrafish larva and explore the characteristics of the first generation teeth by fluoride treatment. MATERIALS AND METHODS: After the zebrafish eggs were laid, they were exposed to excess fluoride (19ppm, 38ppm and 76ppm) for five days. The morphological characteristics of first generation teeth were examined by H&E staining, whole-mount alizarin red and alcian blue staining, and scanning electron microscope (SEM) technique. RESULTS: With whole-mount alizarin red and alcian blue staining, the tooth cusps presented red in normal control. 19ppm and 38ppmm fluoride resulted in extensive red staining from tooth cusps to the lower 1/3 of teeth. 76ppm fluoride caused malformed teeth with uneven red staining. H&E staining showed that excess fluoride caused cystic-like changes in 38ppm and 76ppm groups. SEM revealed the dose dependent pathological changes in zebrafish enameloid with fluoride treatment. Based on SEM findings, we set 0-4 dental fluorosis index (DFI) score to label the severity of dental fluorosis. CONCLUSIONS: Excess fluoride presented a dose dependent fluorosis changes in the teeth of zebrafish larva. The DFI scores in our experiment reflect dose dependent fluorosis changes in a good way and will benefit the future research of dental fluorosis.

ClC-7 Deficiency Impairs Tooth Development and Eruption.

CLCN7 gene encodes the voltage gated chloride channel 7 (ClC-7) in humans. The mutations in CLCN7 have been associated with osteopetrosis in connection to the abnormal osteoclasts functions. Previously, we found that some osteopetrosis patients with CLCN7 mutations suffered from impacted teeth and root dysplasia. Here we set up two in vivo models under a normal or an osteoclast-poor environment to investigate how ClC-7 affects tooth development and tooth eruption. Firstly, chitosan-Clcn7-siRNA nanoparticles were injected around the first maxillary molar germ of newborn mice and caused the delay of tooth eruption and deformed tooth with root dysplasia. Secondly, E13.5 molar germs infected with Clcn7 shRNA lentivirus were transplanted under the kidney capsule and presented the abnormal changes in dentin structure, periodontal tissue and cementum. All these teeth changes have been reported in the patients with CLCN7 mutation. In vitro studies of ameloblasts, odontoblasts and dental follicle cells (DFCs) were conducted to explore the involved mechanism. We found that Clcn7 deficiency affect the differentiation of these cells, as well as the interaction between DFCs and osteoclasts through RANKL/OPG pathway. We conclude that ClC-7 may affect tooth development by directly targeting tooth cells, and regulate tooth eruption through DFC mediated osteoclast pathway.