- Email: [email protected]
The safety and toxicity of food-related titanium dioxide nanoparticle
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ChinaNanomedicine Abstracts / Nanomedicine: Nanotechnology, Biology, and Medicine 12 (2016) 449–575
structures that can integrate multiple functions in an individual vehicle. In our research progress, we have constructed series of micelles self-assembled from polyurethanes with diverse features. The most representative nanodevice is the one synthesized from biodegradable poly(ε-caprolactone) (PCL) and l-lysine ethyl ester diisocyanate (LDI), further extended by 1,4-butandiol (BDO), bis(2-hydroxyethyl) disulfide (DHDS), gemini quaternary ammonium diamine (GQA) and l-lysine-derivative tripeptide diamine containing active carboxyl groups (LGG), and finally terminated by a detachable methoxyl-poly(ethylene glycol) with an acid-labile hydrazone linkage. The PEG as hydrophilic shell could prolong the circulation time in blood and be detached after these nanocarriers accumulated in the tumor sites by enhanced permeability and retention (EPR) effect. Then the cationic gemini quaternary ammonium (GQA) and targeted molecules (monoclonal antibody) conjugated to carboxyl groups of LGG were exposed to strengthen tumor penetration and increase cellular uptake respectively. Finally hydrophobic core wrapped drugs were burst as result of the cleavage of disulfide bonds triggered by intracellular levels of glutathione (GSH) to release the payloads. Moreover these drug delivery systems based on pH-sensitive polyurethanes could successfully escape endosome in responsiveness to the stimulation of acidic organelles. In addition, other strategies such as utilizing phospholipids segments to consolidate in vivo stability, introducing reactive groups for click chemistry to optimize modification methods or preparation blend micelles were also investigated. These drug delivery systems are expected to present a compelling future opportunity to achieve personalized therapy and programmed drug delivery for cancer.
Ag2S quantum dot: A bright and biocompatible fluorescent nanoprobe in the second near-infrared window for in vivo imaging Qiangbin Wang, Key Laboratory of Nano-Bio Interface, Suzhou Institute of Nano-Tech and Nano-Bionics, Chinese Academy of Sciences, Suzhou, China E-mail address: [email protected] (Q. Wang) Fluorescent imaging in the second near-infrared window (NIR-II, 1.0-1.4 μm) is appealing due to minimal autofluorescence and negligible tissue scattering in this region, affording maximal penetration depth for deep tissue imaging with high feature fidelity. Herein, for the first time, we reported a new type of NIR QDs, Ag2S QDs, with emission in the NIR-II region and executed a series of bioapplication studies by using Ag2S QDs. Firstly, highly selective in vitro targeting and imaging of different cell lines were achieved using biocompatible NIR-II Ag2S QDs with different targeting ligand. Secondly, in vivo imaging of early-stage tumor in mice with Ag2S QDs was also achieved. Video-rate dynamic contrast-enhanced imaging revealed deep inner organs and tumor in mice. Thirdly, in vivo real-time visualization of lymphatic structures, blood flow, and angiogenesis mediated by a subcutaneous xenograft 4 T1 mammary tumor were achieved utilizing Ag2S QDs, which helps the future drug development and tumor therapy. Lastly, we systematically studied the biocompatiblity of Ag2S QDs. It turns out that the PEGylated-Ag2S QDs are mainly accumulated in the reticuloendothelial system (RES) including liver and spleen after intravenous administration and can be gradually cleared, mostly by fecal excretion, without appreciable toxicity to the treated mice over a period of 2 months as evidenced by blood biochemistry, hematological analysis and histological examinations.
http://dx.doi.org/10.1016/j.nano.2015.12.051 http://dx.doi.org/10.1016/j.nano.2015.12.053 Delivery of siRNA with nanoparticles based on PEG–PLA block polymer for cancer therapy Jun Wang, The CAS Key Laboratory of Innate Immunity and Chronic Disease, Medical Center and School of Life Sciences, University of Science and Technology of China, Hefei, Anhui, China E-mail address: [email protected] (J. Wang)
The safety and toxicity of food-related titanium dioxide nanoparticle Yun Wang, Zhangjian Chen, Yixuan Ye, Jing Wang, Yao Wu, Hao Zhang, Yihui Wang, Te Ba, Lin Zhuo, Shi Chen, Guang Jia, Department of Occupational and Environmental Health Sciences, School of Public Health, Peking University, Beijing, China E-mail address: [email protected] (Y. Wang)
Small interfering RNA (siRNA) has been rapidly developed as a promising candidate for treatment of numerous diseases. However, clinical application of RNA interference is limited by the delivery of siRNA in vivo. We have developed nanoparticle system with stealthy property for efficient siRNA encapsulation and delivery, which is fabricated with poly(ethylene glycol)-bpoly(d,l-lactide) (PEG–PLA), siRNA and a cationic lipid, using a double emulsion-solvent evaporation technique. Such formulation exhibited high encapsulation efficiency of siRNA, significant down-regulation of gene expression in vivo, and was used for anti-tumor treatments. To more efficiently down-regulate gene expression in solid tumor, such nanoparticles should be more effectively internalized by tumor cells, escaped from the endosome/ lysosome and released the cargo in cells, and we further improved its efficacy via integrating different strategies using block copolymer of PEG and PLA. Firstly, we synthesized block copolymer of PEG and PLA bridged with a linkage responsive to the tumor acidity, and fabricated nanoparticles, which deshielded the PEG layer at the slightly acidic tumor extracellular microenvironment and facilitated the delivery of siRNA to tumor cells after accumulation at the tumor site. Secondly, by incorporating highly membraneactive cationic helical polypeptides to the internal aqueous phase during the nanoparticle preparation process, we significant improved the endosomal escape of nanoparticles. Moreover, we observed that replacing PLA block with poly(lactide-co-glycolide) (PLGA) block promoted intracellular siRNA release. Our results demonstrated that integrating these strategies significantly improved the down-regulation of oncogene expression with specific siRNA in tumor, and substantially reduced the dose of injected siRNA to achieve similar efficacy in tumor growth inhibition when compared with our previous nanoparticle system.
Titanium dioxide nanoparticles (TiO2 NPs) have potential applications as food additives, but concerns persist about their safety. The children are identified as having the highest exposures and may face the greatest health risks, because TiO2 content of sweets is higher than other food products. It is urgent to understand the toxicological properties of TiO2 NPs. Here, a comprehensive toxicity study of TiO2 NPs (75 ± 15 nm, anatase) in Sprague–Dawley rats is reported following oral exposure at dose of 0-200 mg/kg body weight per day for 30 days and 90 days. Although no obvious changes of the Ti contents were found in blood, liver, kidney and spleen among different groups by ICP-MS analysis, TiO2 NPs could induce liver, kidney, heart and blood injuries (white blood cells and red blood cells) in rats. The liver is the most sensitive target organ for TiO2 NPs toxicity by the oral routes. Furthermore, the oral toxicity of TiO2 NPs exhibited the following characteristics: high-dose N low-dose exposure, 90 days N 30 days exposure, male rats N female rats, young rats N adult rats, and gastric ulcer rats N normal rats. Combined ingestion of TiO2 NPs and glucose could cause more severe toxic effects than TiO2 NPs alone, which was attribute to the interaction of TiO2 NPs with glucose and the toxicity of excess glucose. TiO2 NPs were observed in the mucosa of stomach and small intestine tissues by TEM images, meanwhile, non-allergic mast cell activation in stomach tissues and a decrease in the intestinal permeability were found in rats. TiO2 NPs also could affect nutrient absorption, especially of glucose, amino acids and trace elements absorption. On the other hand, a comprehensive genotoxic evaluation of TiO2 NPs was presented, and TiO2 NPs were shown to be genotoxic both in vivo and in vitro tests. The gene mutation and DNA strand breaks seem to be more sensitive genetic endpoints for the detection of TiO2 NPs induced genotoxic effects. These results seem to suggest that it might be prudent to control the application of TiO2 NPs as food additives and limit the ingestion of TiO2 NPs through nonessential foods.
http://dx.doi.org/10.1016/j.nano.2015.12.052
http://dx.doi.org/10.1016/j.nano.2015.12.054
ChinaNanomedicine Abstracts / Nanomedicine: Nanotechnology, Biology, and Medicine 12 (2016) 449–575
structures that can integrate multiple functions in an individual vehicle. In our research progress, we have constructed series of micelles self-assembled from polyurethanes with diverse features. The most representative nanodevice is the one synthesized from biodegradable poly(ε-caprolactone) (PCL) and l-lysine ethyl ester diisocyanate (LDI), further extended by 1,4-butandiol (BDO), bis(2-hydroxyethyl) disulfide (DHDS), gemini quaternary ammonium diamine (GQA) and l-lysine-derivative tripeptide diamine containing active carboxyl groups (LGG), and finally terminated by a detachable methoxyl-poly(ethylene glycol) with an acid-labile hydrazone linkage. The PEG as hydrophilic shell could prolong the circulation time in blood and be detached after these nanocarriers accumulated in the tumor sites by enhanced permeability and retention (EPR) effect. Then the cationic gemini quaternary ammonium (GQA) and targeted molecules (monoclonal antibody) conjugated to carboxyl groups of LGG were exposed to strengthen tumor penetration and increase cellular uptake respectively. Finally hydrophobic core wrapped drugs were burst as result of the cleavage of disulfide bonds triggered by intracellular levels of glutathione (GSH) to release the payloads. Moreover these drug delivery systems based on pH-sensitive polyurethanes could successfully escape endosome in responsiveness to the stimulation of acidic organelles. In addition, other strategies such as utilizing phospholipids segments to consolidate in vivo stability, introducing reactive groups for click chemistry to optimize modification methods or preparation blend micelles were also investigated. These drug delivery systems are expected to present a compelling future opportunity to achieve personalized therapy and programmed drug delivery for cancer.
Ag2S quantum dot: A bright and biocompatible fluorescent nanoprobe in the second near-infrared window for in vivo imaging Qiangbin Wang, Key Laboratory of Nano-Bio Interface, Suzhou Institute of Nano-Tech and Nano-Bionics, Chinese Academy of Sciences, Suzhou, China E-mail address: [email protected] (Q. Wang) Fluorescent imaging in the second near-infrared window (NIR-II, 1.0-1.4 μm) is appealing due to minimal autofluorescence and negligible tissue scattering in this region, affording maximal penetration depth for deep tissue imaging with high feature fidelity. Herein, for the first time, we reported a new type of NIR QDs, Ag2S QDs, with emission in the NIR-II region and executed a series of bioapplication studies by using Ag2S QDs. Firstly, highly selective in vitro targeting and imaging of different cell lines were achieved using biocompatible NIR-II Ag2S QDs with different targeting ligand. Secondly, in vivo imaging of early-stage tumor in mice with Ag2S QDs was also achieved. Video-rate dynamic contrast-enhanced imaging revealed deep inner organs and tumor in mice. Thirdly, in vivo real-time visualization of lymphatic structures, blood flow, and angiogenesis mediated by a subcutaneous xenograft 4 T1 mammary tumor were achieved utilizing Ag2S QDs, which helps the future drug development and tumor therapy. Lastly, we systematically studied the biocompatiblity of Ag2S QDs. It turns out that the PEGylated-Ag2S QDs are mainly accumulated in the reticuloendothelial system (RES) including liver and spleen after intravenous administration and can be gradually cleared, mostly by fecal excretion, without appreciable toxicity to the treated mice over a period of 2 months as evidenced by blood biochemistry, hematological analysis and histological examinations.
http://dx.doi.org/10.1016/j.nano.2015.12.051 http://dx.doi.org/10.1016/j.nano.2015.12.053 Delivery of siRNA with nanoparticles based on PEG–PLA block polymer for cancer therapy Jun Wang, The CAS Key Laboratory of Innate Immunity and Chronic Disease, Medical Center and School of Life Sciences, University of Science and Technology of China, Hefei, Anhui, China E-mail address: [email protected] (J. Wang)
The safety and toxicity of food-related titanium dioxide nanoparticle Yun Wang, Zhangjian Chen, Yixuan Ye, Jing Wang, Yao Wu, Hao Zhang, Yihui Wang, Te Ba, Lin Zhuo, Shi Chen, Guang Jia, Department of Occupational and Environmental Health Sciences, School of Public Health, Peking University, Beijing, China E-mail address: [email protected] (Y. Wang)
Small interfering RNA (siRNA) has been rapidly developed as a promising candidate for treatment of numerous diseases. However, clinical application of RNA interference is limited by the delivery of siRNA in vivo. We have developed nanoparticle system with stealthy property for efficient siRNA encapsulation and delivery, which is fabricated with poly(ethylene glycol)-bpoly(d,l-lactide) (PEG–PLA), siRNA and a cationic lipid, using a double emulsion-solvent evaporation technique. Such formulation exhibited high encapsulation efficiency of siRNA, significant down-regulation of gene expression in vivo, and was used for anti-tumor treatments. To more efficiently down-regulate gene expression in solid tumor, such nanoparticles should be more effectively internalized by tumor cells, escaped from the endosome/ lysosome and released the cargo in cells, and we further improved its efficacy via integrating different strategies using block copolymer of PEG and PLA. Firstly, we synthesized block copolymer of PEG and PLA bridged with a linkage responsive to the tumor acidity, and fabricated nanoparticles, which deshielded the PEG layer at the slightly acidic tumor extracellular microenvironment and facilitated the delivery of siRNA to tumor cells after accumulation at the tumor site. Secondly, by incorporating highly membraneactive cationic helical polypeptides to the internal aqueous phase during the nanoparticle preparation process, we significant improved the endosomal escape of nanoparticles. Moreover, we observed that replacing PLA block with poly(lactide-co-glycolide) (PLGA) block promoted intracellular siRNA release. Our results demonstrated that integrating these strategies significantly improved the down-regulation of oncogene expression with specific siRNA in tumor, and substantially reduced the dose of injected siRNA to achieve similar efficacy in tumor growth inhibition when compared with our previous nanoparticle system.
Titanium dioxide nanoparticles (TiO2 NPs) have potential applications as food additives, but concerns persist about their safety. The children are identified as having the highest exposures and may face the greatest health risks, because TiO2 content of sweets is higher than other food products. It is urgent to understand the toxicological properties of TiO2 NPs. Here, a comprehensive toxicity study of TiO2 NPs (75 ± 15 nm, anatase) in Sprague–Dawley rats is reported following oral exposure at dose of 0-200 mg/kg body weight per day for 30 days and 90 days. Although no obvious changes of the Ti contents were found in blood, liver, kidney and spleen among different groups by ICP-MS analysis, TiO2 NPs could induce liver, kidney, heart and blood injuries (white blood cells and red blood cells) in rats. The liver is the most sensitive target organ for TiO2 NPs toxicity by the oral routes. Furthermore, the oral toxicity of TiO2 NPs exhibited the following characteristics: high-dose N low-dose exposure, 90 days N 30 days exposure, male rats N female rats, young rats N adult rats, and gastric ulcer rats N normal rats. Combined ingestion of TiO2 NPs and glucose could cause more severe toxic effects than TiO2 NPs alone, which was attribute to the interaction of TiO2 NPs with glucose and the toxicity of excess glucose. TiO2 NPs were observed in the mucosa of stomach and small intestine tissues by TEM images, meanwhile, non-allergic mast cell activation in stomach tissues and a decrease in the intestinal permeability were found in rats. TiO2 NPs also could affect nutrient absorption, especially of glucose, amino acids and trace elements absorption. On the other hand, a comprehensive genotoxic evaluation of TiO2 NPs was presented, and TiO2 NPs were shown to be genotoxic both in vivo and in vitro tests. The gene mutation and DNA strand breaks seem to be more sensitive genetic endpoints for the detection of TiO2 NPs induced genotoxic effects. These results seem to suggest that it might be prudent to control the application of TiO2 NPs as food additives and limit the ingestion of TiO2 NPs through nonessential foods.
http://dx.doi.org/10.1016/j.nano.2015.12.052
http://dx.doi.org/10.1016/j.nano.2015.12.054