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Liu, Juan; Ma, Xiaowei; Lei, Chunni; Xue, Xiangdong; Wei, Tuo; Zhao, Jing; Li, Shuyi; Liang, Xing-Jie
doi: 10.1039/c6tb00761apmid: 32263083
We developed a novel self-assembled DNA nanostructure for anticancer drug delivery. The resulting nanostructure was able to specifically target cancer cells and release the loaded drug at pH 5.0. More importantly, the drug-loaded DNA nanostructure effectively circumvented doxorubicin resistance of human lung adenocarcinoma epithelial cancer cells.
doi: 10.1039/c6tb00330cpmid: 32263084
Hydrogels composed of designed β-sheet amphiphilic peptides have been exploited in controlled drug release systems, tissue regeneration and bleeding arrest applications. However the ultimate function of these hydrogels is dependent on a variety of host tissue responses, including blood clotting mechanisms. Here we studied the effect of cationic, anionic and zwitterionic β-sheet amphiphilic peptides on platelet-poor plasma (PPP) coagulation. PPP clotting was monitored by thromboelastography (TEG) in two states: low peptide concentration, dissolved in plasma, and high peptide concentration, assembled in a hydrogel phase. In the dissolved state the positively charged peptide led to immediate phase separation of PPP. The dissolved zwitterionic peptide exhibited minor effects on clotting and essentially no influence in the hydrogel state. The negatively charged peptide in the dissolved state and as a hydrogel retarded fibrin formation and reduced clot strength. This peptide was also found to inhibit blood clotting in spleen wounds in rats, by both interacting with thrombin and depleting Ca2+ from blood. This study demonstrates a systematic approach towards characterization of the effects of self-assembled biomaterials on coagulation in vitro, shedding light on the structure–function relationship useful for the design of new implantable biomaterials.
Yang, Jingmei; Duan, Yongchao; Zhang, Xuezhu; Wang, Yongjian; Yu, Ao
doi: 10.1039/c6tb00847jpmid: 32263085
Stimuli-responsive drug release nanoparticles are of particular interest due to their enhanced effects and reduced systemic toxicities in the area of cancer therapeutics. The effect of these nanoparticles on the cellular microenvironment has not yet been clearly defined. In this context, redox-responsive nanoparticles were synthesized with disulfide-containing linkages. These nanoparticles depleted the cellular GSH level and modulated the cellular redox microenvironment to more oxidizing conditions. The resulting drug-encapsulated nanoparticles showed improved cytotoxicity, apoptosis, and invasion inhibition of metastatic cancer cells. Moreover, these improvements had a direct correlation with the cellular redox status modulated by nanoparticles. The present study provides a new strategy for designing redox-responsive drug carriers to improve the sensitivity of cells to anticancer drugs and enhance the therapeutic efficacy in metastatic cancer.
Jampaiah, Deshetti; Srinivasa Reddy, T.; Kandjani, Ahmad Esmaielzadeh; Selvakannan, P. R.; Sabri, Ylias M.; Coyle, Victoria E.; Shukla, Ravi; Bhargava, Suresh K.
doi: 10.1039/c6tb00422apmid: 32263086
The construction of highly efficient inorganic mimetic enzymes (nanozymes) is much needed to replace natural enzymes due to their instability and high cost. Recently, nanoscale CeO2 has been attracting significant interest due to its unique properties such as facile redox behaviour (Ce4+ ↔ Ce3+) and surface defects. In the present work, various amounts of Fe3+-doped CeO2 nanorods (NRs) (with 3, 6, 9, and 12% Fe doping) were synthesized using a facile hydrothermal method and investigated for peroxidase-like activity and glucose detection. The peroxidase-like activity results revealed that 6 at% doping is the optimal Fe doping level to demonstrate superior catalytic performance over un-doped and Fe3+-doped CeO2 NRs. Steady state kinetic analysis also confirms that the 6% Fe3+-doped CeO2 (6Fe/CeO2) NRs exhibited excellent catalytic performance towards 3,3′,5,5′tetramethylbenzidine (TMB) oxidation with a Km and Vm of 0.176 mM and 8.6 × 10−8 M s−1, respectively, as compared to horseradish peroxidase (HRP) enzymes (0.434 mM and 10.0 × 10−8 M s−1). Typical colour reactions arising from the catalytic oxidation of the TMB substrate over 6Fe/CeO2 NRs with H2O2 have been utilized to establish a simple sensitive and selective colorimetric assay for the determination of glucose concentration in buffer, diluted fruit juices and foetal bovine serum samples. The superior catalytic performance of 6Fe/CeO2 NRs could be attributed to abundant surface defects, high surface area and pore volume, and preferential exposure of the highly reactive (110) planes.
Lam, Zhiyong; Balasundaram, Ghayathri; Kong, Kien Voon; Chor, Bo Yang; Goh, Douglas; Khezri, Bahareh; Webster, Richard D.; Leong, Weng Kee; Olivo, Malini
doi: 10.1039/c6tb00075dpmid: 32263087
High nuclearity carbonyl clusters of ruthenium and osmium are found to exhibit good photoacoustic (PA) activity in the near-IR (NIR) region. Their potential as PA contrast agents for full body imaging has been demonstrated for the first time with mice; intravenous administration of the osmium carbonyl cluster Na2[Os10(μ6-C)(CO)24] afforded up to a four-fold enhancement of the PA signal in various tissues. The cluster exhibits low toxicity, high stability and superior PA stability compared to the clinically approved NIR dye, indocyanine green.
Ma, Chin-Tsu; Wu, Yi-Jhen; Huang, Han Hsiang; Kang, Pei-Leun; Hsiao, Kuan Yin; Lo, Dan Yuan; Kuo, Shyh Ming
doi: 10.1039/c6tb00731gpmid: 32263088
Advances and improvements in mesenchymal stromal/stem cells (MSCs) and cell replacement therapies have been promising approaches to treat diabetes mellitus (DM) since their potent capacities for differentiation into various functional cells match the demands of tissue repair and regeneration. The aim of this study is to examine the effects of nano-sized type I collagen molecules in combination with nicotinamide (NCT) and exendin-4 (EX4) on MSC differentiation into insulin-secreting cells in vitro and to evaluate their reparative effects against type 2 diabetes mellitus (T2DM) in vivo. Differentiation of MSCs in the presence of NCT, nano-sized type I collagen molecules and EX4 was represented with insulin production and Nkx6.1/PDX-1 mRNA expression assessed by insulin secretion assay and quantitative RT-PCR. Histopathological and glycosylated haemoglobin (HbA1) analysis was performed to assess reparative effects against T2DM in the rat model. The results revealed that MSCs showed increased differentiation into insulin-secreting cells with higher mRNA expression for Nkx6.1 and early PDX-1 in the presence of NCT and nano-sized type I collagen molecules. Addition of nano-sized type I collagen fibrils increased morphologically islet-like clusters in differentiated cells. T2DM rats reverted to their normal HbA1 values and exhibited structurally repaired islets in the pancreas implanted with NCT/nano-sized collagen I molecule/EX4-incubated differentiated cells. In short, the combined recipe showed reparative actions on the destructive islet of Langerhans in the pancreas coupled with glucoregulatory effects in T2DM rats in vivo. Therefore, MSCs incubated with NCT/EX4 and nano-sized collagen I molecules could be a potential therapy for retrieval of destructed islets and could efficiently regulate blood glucose in T2DM.
Zhu, Genxing; Zhao, Ruibo; Li, Yaling; Tang, Ruikang
doi: 10.1039/c5tb02767epmid: 32263089
Multifunctional Gd,Ce,Tb co-doped β-tricalcium phosphate (TCP) porous nanospheres are prepared by a facile solvothermal strategy with trimethyl phosphate as the phosphorus source. The as-prepared nanomaterial (average diameter of 100 nm) has a multiple level pore size distribution with the specific surface area of 124.33 m2 g−1, which benefits drug loading. Its photoluminescent and magnetic multifunctions are realized by the co-doping of Gd3+, Ce3+ and Tb3+ ions, which make the nanomaterial promising for both fluorescence and magnetic resonance imaging techniques. Furthermore, the nanomaterial exhibits excellent cytocompatibility and a relatively high doxorubicin loading capacity as well as sustained pH-sensitive drug release behaviour. It is suggested that the Gd,Ce,Tb co-doped β-TCP porous nanospheres are promising for applications in the biomedical fields such as multifunctional drug delivery systems and tissue engineering scaffolds with bioimaging guidance.
doi: 10.1039/c6tb00680apmid: 32263090
A highly selective ratiometric ESIPT fluorescent probe has been designed for the detection of palladium species of all the typical oxidation states (0, +2, +4). The probe exhibits a ratiometric fluorescence response towards the palladium species in about 20 min at room temperature based on the excited state intramolecular proton transfer (ESIPT) process. Moreover, the probe can discriminate different palladium species (Pd0, Pd2+, Pd4+) under different detection conditions. Furthermore, the probe can be used to quantitatively detect palladium in drinking water with a low detection limit (15.6 nM, 1.66 ppb). Additionally, it could be used as a two-photon palladium probe for bioimaging with low cytotoxicity and autofluorescence.
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