International Journal of Nanomedicine
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2022
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IF 7.033
Nan Liu,Yi Guan,Chunling Zhou,Yongheng Wang,Zhanfei Ma,Sanqiao Yao
Purpose The main objective of this study was to clarify the biodistribution and in vivo toxicological effects of indium-tin oxide nanoparticles (Nano-ITO) in male rats.Methods Dose-response (three divided doses) and time-course studies (six exposure durations) were performed to examine Nano‑ITO-induced pulmonary and systemic toxicity. At the end of the experiment, hematology and serum biochemical parameters were determined, and cytokines levels and oxidative stress were analyzed in the bronchoalveolar lavage fluid. In addition, indium biodistribution following Nano‑ITO exposure was determined using inductively coupled plasma mass spectrometer to measure indium concentration in the lung, spleen, brain, liver, kidney, and testis. Rat lung tissues were also harvested for staining with hematoxylin and eosin, periodic acid Schiff stain, Masson’s trichrome, and Sirius red.Results Relative lung weights were significantly increased in all Nano-ITO-exposed groups. All organs exhibited a statistically significant difference in indium levels. Rat exposure to Nano‑ITO resulted in a dose-response increase in acute systemic inflammation and injury. BALF analysis revealed significantly elevated levels of lung oxidative stress, pulmonary injury, and inflammatory markers across most groups. Serum biochemistry results showed that Nano-ITO could affect the liver and renal functions of rats when exposed for 3 days. Compared with the control group, significant inflammatory responses or pathological changes were observed in the liver, kidney, and testis of rats at different sampling times and three doses examined. Histopathologically, foci of slight-to-severe pulmonary inflammatory response along with acute inflammatory, pulmonary fibrosis and alveolar proteinosis were detected, and the severity of these lesions worsened in a dose- and time-dependent manner.Discussion These findings provide novel evidence that enhanced progressive massive pulmonary fibrosis, diffuse interstitial fibrosis, and collagen accumulation play a role in the development of pulmonary alveolar proteinosis following Nano-ITO exposure.
研究领域:
纳米技术
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毒理学
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肺病学
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病理学
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DOI
PubMed
高影响因子
Journal of the Mechanical Behavior of Biomedical Materials
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2023
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IF 3.9
Rongfang Zou,Lunan Bi,Yang Huang,Yadi Wang,Yan Wang,Lin Li,Jiayin Liu,Lu Feng,Xiaoxia Jiang,Bin Deng
For decades, titanium has been the preferred material for dental implant fabrication. However, metallic ions and particles can cause hypersensitivity and aseptic loosening. The growing demand for metal-free dental restorations has also promoted the development of ceramic-based dental implants, such as silicon nitride . In this study, silicon nitride (Si 3 N 4 ) dental implants were fabricated for biological engineering by photosensitive resin based digital light processing (DLP) technology, comparable to conventionally produced Si 3 N 4 ceramics. The flexural strength was (770 ± 35) MPa by the three-point bending method, and the fracture toughness was (13.3 ± 1.1) MPa · m 1/2 by the unilateral pre-cracked beam method. The elastic modulus measured by the bending method was (236 ± 10) GPa. To confirm whether the prepared Si 3 N 4 ceramics possessed good biocompatibility , in vitro biological experiments were performed with the fibroblast cell line L-929, and preferable cell proliferation and apoptosis were observed at the initial stages. Hemolysis test, oral mucous membrane irritation test, and acute systemic toxicity test (oral route) further confirmed that the Si 3 N 4 ceramics did not exhibit hemolysis reaction, oral mucosal stimulation, or systemic toxicity. The findings indicate that Si 3 N 4 dental implant restorations with personalized structures prepared by DLP technology have good mechanical properties and biocompatibility, which has great application potential in the future.
研究领域:
牙科材料
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生物医学工程
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材料科学
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生物相容性测试
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DOI
PubMed
高影响因子
International Journal of Nanomedicine
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2024
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IF 6.6
Dan Wang,Xiaobo Wang,Yan Li,Xiaowei Wang,Xuelei Wang,Jiayi Su,Apeng Wang,Kai Lv,Mingliang Liu,Guimin Xia
Background Gemcitabine (Gem) is one of the first-line chemotherapy drugs for pancreatic cancer treatment. However, its short half-life in plasma and adverse effects limited its broader application.Methods A novel Gem derivative (N4-tetradecyloxycarbonyl gemcitabine, tcGem) was synthesized and encapsulated into liposomes (LipotcGem) to overcome the above shortcomings.Results LipotcGem has been successfully formulated, with the average size of 115 nm, zeta potential values of −36 mV, encapsulation efficiency of up to 98%, and drug loading capacity of 8.1%. Compared to Gem, LipotcGem improved in vitro antitumor activity significantly, as evidenced by the lower IC50, the higher percentage of apoptotic cells, the stronger ability to inhibit cell migration and invasion due to the higher cellular accumulation (100 times). Additionally, the endocytosis of LipotcGem was mainly mediated by caveolae, and was then processed in the lysosome, where tcGem was released and hydrolyzed into Gem. LipotcGem inhibited tumor growth by 70% in subcutaneous xenograft model and 90% in orthotopic xenograft model, respectively. LipotcGem suppressed tumor metastasis and prolonged survival without perceptible systemic toxicity, which may be caused by the longer t1/2 in vivo (3.5 times, 5.23 vs 1.46 h) and more enrichment in tumor tissue (750 times).Conclusion LipotcGem significantly increased the anti-tumor efficiency and decreased the toxicity for chemotherapy of pancreatic cancer.
研究领域:
肿瘤学
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药学
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药物递送系统
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癌症研究
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PubMed
高影响因子
Science Advances
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2020
·Vol. 6
·期 45
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IF 13.117
Yinxian Yang,Bingjun Sun,Shiyi Zuo,Ximu Li,Shuang Zhou,Lingxiao Li,Cong Luo,Hongzhuo Liu,Maosheng Cheng,Yongjun Wang,Shujun Wang,Zhonggui He,Jin Sun
Rational design of nanoparticulate drug delivery systems (nano-DDS) for efficient cancer therapy is still a challenge, restricted by poor drug loading, poor stability, and poor tumor selectivity. Here, we report that simple insertion of a trisulfide bond can turn doxorubicin homodimeric prodrugs into self-assembled nanoparticles with three benefits: high drug loading (67.24%, w/w), high self-assembly stability, and high tumor selectivity. Compared with disulfide and thioether bonds, the trisulfide bond effectively promotes the self-assembly ability of doxorubicin homodimeric prodrugs, thereby improving the colloidal stability and in vivo fate of prodrug nanoassemblies. The trisulfide bond also shows higher glutathione sensitivity compared to the conventional disulfide bond, and this sensitivity enables efficient tumor-specific drug release. Therefore, trisulfide bond–bridged prodrug nanoassemblies exhibit high selective cytotoxicity on tumor cells compared with normal cells, notably reducing the systemic toxicity of doxorubicin. Our findings provide new insights into the design of advanced redox-sensitive nano-DDS for cancer therapy.
研究领域:
药学
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纳米技术
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癌症研究
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药物递送系统
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DOI
PubMed
高影响因子
ACS Applied Bio Materials
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2019
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IF 0
Yuan-Fu Ding,Tianlei Sun,Shengke Li,Qiaoxian Huang,Ludan Yue,Liangkui Zhu,Ruibing Wang
Orally administered colon-targeted formulations of drugs are of great importance in managing diseases in the colon. However, it is often challenging to maintain the integrity of such formulations during delivery, particularly in the gastric environment, which may lead to premature drug release before reaching the targeted colon. Herein, an oral colon-targeted drug delivery hydrogel (OCDDH) was developed through cucurbit[8]uril (CB[8])-mediated noncovalent cross-linking of phenylalanine (Phe)-modified Konjac glucomannan (KGM), in which berberine (BBR), a natural anti-inflammatory product originating from Chinese medicine, was loaded into the hydrogel matrix. With the strong host–guest complexation mediated cross-linking and the inherent reversibility of such interactions, KGM-Phe@CB[8] hydrogel exhibited a readily tunable degree of cross-linking and an excellent self-healing capability, and therefore the hydrogel retained ultrahigh stability in the gastric environment, which is important for orally administered formulations to target the colon. In the colon, KGM may get degraded by colon-specific enzymes, β-mannanase or β-glucosidase, resulting in burst release of the loaded cargoes on site. The structure and specific payload release of the hydrogel, with and without BBR, have been fully characterized in vitro, and the therapeutic effect of BBR-loaded KGM-Phe@CB[8] hydrogel was evaluated against dextran sulfate sodium (DSS) induced ulcerative colitis (UC) in a mouse model. Very interestingly, the BBR-loaded KGM-Phe@CB[8] hydrogel exhibited significantly improved therapeutic efficacy in treating colitis, without causing any systemic toxicity, when compared with free BBR. This strategy may pave a new way in the development of advanced supramolecular OCDDH.
研究领域:
药学
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药物递送系统
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结直肠疾病
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超分子化学
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DOI
PubMed
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