DRUG DEVELOPMENT AND INDUSTRIAL PHARMACY
·
2015
·
IF 2.101
Qiang Xu,Tao Zhu,Chaoli Yi,Qi Shen
Considered a popular drug for diabetes in recent years, metformin was determined to have a moderate anti-tumor effect, particularly in breast cancer. In this study, the anticancer mechanism of metformin was verified by preparing solid lipid nanoparticles (SLNs) and chitosan-modified solid lipid nanoparticles (CSLNs) containing metformin and then estimating the potential of these SLNs for uptake in cells and mitochondria. Metformin–SLNs were prepared using an emulsification and low-temperature solidification method. The mean particle size, zeta potential, entrapment efficiency, and loading efficiency of metformin–SLNs and metformin chitosan-modified SLNs were 102.3 ± 4.16 and 200.1 ± 17.69 nm, –21.25 ± 4.89 and 50.6 ± 4.09 mv, 26.25 ± 2.59% and 33.6 ± 2.21%, and 1.74 ± 0.16% and 1.46 ± 0.10%, respectively.TEM images showed that both the nanoparticles had spherical morphologies with no aggregation. Results of cellular and mitochondrial uptake showed that the metformin–SLNs were easier to uptake in cells and mitochondria than the pure drug group (that was the control group without SLN structure modification). The findings of this research provide a basis for conducting further studies on the anticancer mechanism of metformin.
研究领域:
药剂学
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肿瘤学
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纳米医学
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DOI
高影响因子
Materials
·
2023
·Vol. 16
·期 6
·2277
·
IF 3.4
Si Xu,Shanshan Liang,Bing Wang,Jiali Wang,Meng Wang,Lingna Zheng,Hao Fang,Tingfeng Zhang,Yi Bi,Weiyue Feng
Pre-coating with a protein corona on the surface of nanomaterials (NMs) is an important strategy for reducing non-specific serum protein absorption while maintaining targeting specificity. Here, we present lipoic acid-terminated polyethylene glycol and transferrin bi-functionalized MoS2nanosheets ([email protected]2-PEG NSs) as a feasible approach to enhance cellular uptake.[email protected]2-PEG NSs can maintain good dispersion stability in cell culture medium and effectively protect MoS2NSs from oxidation in ambient aqueous conditions. Competitive adsorption experiments indicate that transferrin was more prone to bind MoS2NSs than bovine serum albumin (BSA). It is noteworthy that single HepG2 cell uptake of[email protected]2-PEG presented a heterogeneous distribution pattern, and the cellular uptake amount spanned a broader range (from 0.4 fg to 2.4 fg). Comparatively, the intracellular Mo masses in HepG2 cells treated with[email protected]2-PEG and MoS2-PEG showed narrower distribution, indicating homogeneous uptake in the single HepG2 cells. Over 5% of HepG2 cells presented uptake of the[email protected]2-PEG over 1.2 fg of Mo, about three-fold that of[email protected]2-PEG (0.4 fg of Mo). Overall, this work suggests that Tf coating enhances the cellular uptake of MoS2NSs and is a promising strategy for improving the intracellular uptake efficiency of cancer cells.Keywords:bi-functionalization;[email protected]2-PEG nanosheets;HepG2 cellular uptake
研究领域:
材料科学
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纳米技术
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生物医学工程
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细胞生物学
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DOI
PubMed
高影响因子
ACS Omega
·
2021
·
IF 3.512
Zhongmin Wang,Ying Li,Taotao Peng,Ying Su,Xiaoting Luo,Wanjun Han,Hongjian Zhang,Jianqing Ruan,Chunshan Gui
Phenolsulfonphthalein (PSP or phenol red), a sulfonphthalein dye, has been used as a diagnostic agent and a pH indicator in cell culture medium. After administered into the body, PSP is excreted into urine and bile. The urinary excretion of PSP is mediated by organic anion transporter 1/3 (OAT1/3) and multidrug resistance protein 2 (MRP2). In biliary excretion, PSP is effluxed from hepatocytes into the bile via MRP2. However, so far, the molecular mechanism for PSP transport from the blood into hepatocytes is unclear. In the present study, six human major hepatic uptake transporters expressed on the basolateral membrane of hepatocytes, namely, organic anion transporting polypeptide 1B1 (OATP1B1), OATP1B3, OATP2B1, Na+/taurocholate cotransporting polypeptide (NTCP), organic cation transporter 1 (OCT1), and OAT2, have been investigated to see whether they are involved in the hepatic uptake of PSP. An in vitro cell-based study demonstrated that PSP is a substrate for OATP1B1, OATP1B3, and OATP2B1, with OATP1B3 showing the highest transport efficiency. The Km values for OATP1B1-, OATP1B3-, and OATP2B1-mediated PSP uptake were 11.3 ± 1.5, 7.0 ± 1.5, and 5.1 ± 1.0 μM, respectively. PSP interacts with known OATP substrates/inhibitors. However, the presence of PSP in cell culture medium has no significant effect on OATP’s function. In vivo pharmacokinetic study in wild-type and Oatp1b2-knockout mice showed that Oatp1b2-knockout led to elevated plasma concentration and decreased liver accumulation of PSP. Taken together, the present study showed that in the liver, OATP1B1, OATP1B3, and OATP2B1 are involved in the uptake of PSP from the blood into hepatocytes, which, along with MRP2-mediated efflux of PSP from hepatocytes into the bile, constitute the vectorial transport of PSP from the blood to the bile and may play a critical role in the biliary excretion of PSP.
研究领域:
药理学
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肝病学
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分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
SCIENCE OF THE TOTAL ENVIRONMENT
·
2021
·
IF 7.963
Hui Lin,Yinqiu Yuan,Xiaoman Jiang,Jian-Ping Zou,Xinghui Xia,Shenglian Luo
Microplastics (MPs) are the significant environmental factor for bioavailability of hydrophobic organic contaminants (HOCs) in aquatic environments. Nevertheless, the bioavailability of microplastic-associated HOCs remains unclear. In this research, the freely dissolved pyrene concentrations were kept stable with passive dosing devices, and the pyrene content in D. magna tissues as well as D. magna immobilization were analyzed to quantify bioavailability of pyrene (a representative HOC) associated with naturally-aged polystyrene (PS) MPs. Furthermore, the uptake mechanisms of pyrene associated with MPs of different sizes were explored by investigating the distribution of MPs in D. magna tissues with scanning electron microscopy. Especially, a new schematic model of bioavailability process was established. The results demonstrated that a part of pyrene associated with 0–1.5 μm MPs could directly cross cell membrane through endocytosis from intestine and exposure solutions to D. magna tissues except the 10–60 and 60–230 μm MPs. The bioavailability of microplastic-associated pyrene was ordered as 0–1.5 μm (20.0–21.6%) > 10–60 μm (10.7–13.8%) > 60–230 μm MPs (6.0–9.8%), which were essentially resulted from the difference in uptake mechanisms of pyrene associated with MPs of different sizes. This work suggests that the bioavailability of microplastic-associated HOCs should be considered when assessing water quality and environmental risk of HOCs in natural waters.
研究领域:
环境科学
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毒理学
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DOI
PubMed
高影响因子
International Journal of Nanomedicine
·
2025
·
IF 6.5
Jiahao Li,Sharon Shui Yee Leung,Edwin Ho Yin Chan,Cuiping Jiang,Evelyn Tze Yin Ho,Zhong Zuo
Introduction Piperine, the major component in Piper retrofractum and Piper nigrum, had potential therapeutic effects on central nervous system diseases such as Alzheimer’s disease, Parkinson’s disease, epilepsy and fragile X-associated tremor/ataxia syndrome. However, its low aqueous solubility (0.04 mg/mL) limits brain uptake and pharmacological investigations at higher doses. In the current study, formulation strategies and routes of administration were assessed to enhance systemic and brain uptake of piperine.Methods Formulation of piperine nanoparticles (PIP NPs) was developed to enhance its solubility. PIP NPs were prepared using flash nanoprecipitation via a four-stream Multi-Inlet Vortex Mixer, employing an aqueous solution of poloxamer 188 and an ethanolic solution containing piperine and Eudragit L100-55. The process was optimized using the Design of Experiments to minimize the particle size and maximize the encapsulation efficiency of piperine. Additionally, we investigated the impact of administrating PIP NPs via oral and intranasal routes on its systemic and brain uptake.Results The optimized PIP NPs formulation exhibited a particle size of 171.45±2.38 nm, polydispersity index of 0.27±0.01, zeta potential of −43.71±5.11 mV, encapsulation efficiency of 92.49±1.92% and drug loading of 15.07±0.09%. Fourier-transform infrared spectroscopy confirmed the successful encapsulation of piperine into nanoparticles. The PIP NPs could significantly increase the aqueous solubility of piperine from 0.04 mg/mL to 52.31±0.9 mg/mL and release piperine with a 12.83-fold higher rate than that from piperine suspension. Both oral and intranasal administrations of PIP NPs to C57BL/6 mice at 20 mg/kg demonstrated an increase in AUC0-120min for both plasma (7.9–10 times) and brain (4.7–5.0 times) comparing to that from piperine suspension, with no significant difference between these two routes.Discussion Our findings suggested that increasing solubility rather than changing the administration route served as the most critical step to enhance the brain uptake of piperine.
研究领域:
药剂学
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神经科学
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药物代谢动力学
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产品关联
DOI
PubMed
高影响因子
Materials
·
2015
·Vol. 8
·期 12
·8701-8713
·
IF 2.651
Kaikai Wang,Juan Wang,Wenwen Hu,Yifan Zhang,Feng Zhi,Zaigang Zhou,Jinhui Wu,Yiqiao Hu
Hemoglobin is a promising drug carrier but lacks extensive investigation. The chemical conjugation of hemoglobin and drugs is costly and complex, so we have developed curcumin-loaded hemoglobin nanoparticles (CCM-Hb-NPs) via self-assembly for the first time. Using the acid-denaturing method, we avoid introducing denaturants and organic solvents. The nanoparticles are stable with uniform size. We have conducted a series of experiments to examine the interaction of hemoglobin and CCM, including hydrophobic characterization, SDS-PAGE. These experiments substantiate that this self-assembly process is mainly driven by hydrophobic forces. Our nanoparticles achieve much higher cell uptake efficiency and cytotoxicity than free CCM solutionin vitro. The uptake inhibition experiments also demonstrate that our nanoparticles were incorporated via the classic clathrin-mediated endocytosis pathway. These results indicate that hemoglobin nanoparticles formed by self-assembly are a promising drug delivery system for cancer therapy.Keywords:drug carrier;hydrophobic forces;self-assemble;cell uptake
研究领域:
生物化学
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药剂学
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肿瘤学
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产品关联
DOI
PubMed
高影响因子
Journal of Materials Chemistry B
·
2024
·Vol. 12
·期 26
·6442-6451
·
IF 6.1
Jia-Hao Bai,Qing-Tao Yu,Yi-Wu Wang,Chun-Fa Chen,Lian-Ju Ma,Yue Yuan,Yong-Jun Gan,Jia-Qi Yang,Shu Zhu,Yu-Hang Ran,Li-Lei Zhang,Hang Qian,Zheng-Huan Zhao,Qian Liu
Self-assembled DNA nanostructures hold great promise in biosensing, drug delivery and nanomedicine. Nevertheless, challenges like instability and inefficiency in cellular uptake of DNA nanostructures under physiological conditions limit their practical use. To tackle these obstacles, this study proposes a novel approach that integrates the cationic polymer polyethyleneimine (PEI) with DNA self-assembly. The hypothesis is that the positively charged linear PEI can facilitate the self-assembly of DNA nanostructures, safeguard them against harsh conditions and impart them with the cellular penetration characteristic of PEI. As a demonstration, a DNA nanotube (PNT) was successfully synthesized through PEI mediation, and it exhibited significantly enhanced stability and cellular uptake efficiency compared to conventional Mg2+-assembled DNA nanotubes. The internalization mechanism was further found to be both clathrin-mediated and caveolin-mediated endocytosis, influenced by both PEI and DNA. To showcase the applicability of this hybrid nanostructure for biomedical settings, the KRAS siRNA-loaded PNT was efficiently delivered into lung adenocarcinoma cells, leading to excellent anticancer effects in vitro. These findings suggest that the PEI-mediated DNA assembly could become a valuable tool for future biomedical applications.
研究领域:
纳米医学
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癌症治疗
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分子生物学
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DOI
PubMed
高影响因子
RSC Advances
·
2017
·Vol. 7
·期 26
·16131-16138
·
IF 3.108
Xinyi Ding,Ning Han,Jun Wang,Yuxiang Sun,Gang Ruan
Micellar nanocrystals (nanocrystal-encapsulated micelles) has become an emerging class of nanomaterials for a wide spectrum of biomedical applications. The most commonly used approach to vary the properties of micellar nanocrystals is using different types or molecular weights of amphiphilic molecules. The present work focuses on investigating the effects of an alternative material parameter, i.e., organic solvent, which primarily affects the kinetics rather than thermodynamics of the formation process, on the structures of the micellar nanocrystal product fabricated by combining electrospray and self-assembly. We find that, compared with chloroform (commonly used in prior works and used as the reference here) as the organic solvent, dichloromethane (DCM, lower boiling point than chloroform) leads to nearly zero encapsulation of nanocrystals in micelles, and tetrahydrofuran (THF, higher water miscibility than chloroform) leads to greatly enhanced encapsulation of nanocrystals in micelles. The use of THF could thus solve the previously identified problem of low nanocrystal encapsulation. Surprisingly, a prolonged fabrication process of micellar nanocrystals with THF is found to generate worm-shaped products. Further study of the formation mechanism of the worm-shaped micelles indicates that they are formed through THF-induced/facilitated fusion of spherical micelles. The thus-formed worm-shaped micellar nanocrystals are found to offer greatly reduced non-specific cellular uptake than the spherical counterparts. These results offer significant insights on micellar nanocrystal, micelle fusion as well as self-assembly, and provide new ways to control the structures of nanomaterials and their biological responses.
研究领域:
材料科学
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生物医学工程
·
纳米技术
✓ 已验证
产品关联
DOI
高影响因子
Acta Pharmaceutica Sinica B
·
2014
·
IF 0
Meihong Huang,Jiaqi Song,Bingzheng Lu,Huizhi Huang,Yizhen Chen,Wei Yin,Wenbo Zhu,Xinwen Su,Chuanbin Wu,Haiyan Hu
In this work, retinal penetration of fluorescein was achieved in vitro by covalent attachment of taurine to fluorescein, yielding the F–Tau conjugate. Nuclear magnetic resonance (NMR) and high resolution mass spectrometry (HRMS) were used to confirm the successful synthesis of F–Tau. The cellular uptake of F–Tau in adult retinal pigment epithelial cells (ARPE-19) and human retinal microvascular endothelial cells (hRMECs) was visualized via confocal scanning microscopy. The results indicated an improvement of solubility and a reduction of log P of F–Tau compared with fluorescein. As compared with fluorescein, F–Tau showed little toxicity, and was retained longer by cells in uptake experiments. F–Tau also displayed higher transepithelial permeabilities than fluorescein in ARPE-19 and hRMECs monolayer cells ( P <0.05). These results showed that taurine may be a useful ligand for targeting small-molecule hydrophobic pharmaceuticals into the retina.
研究领域:
药理学
·
生物化学
·
眼科学
✓ 已验证
DOI
PubMed
COLLOIDS AND SURFACES B-BIOINTERFACES
·
2025
·
IF 5.6
Longyu Wang,Yichen Li,Pingge Jiang,Hao Bai,Chengfan Wu,Qi Shuai,Yunfeng Yan
Lipid nanoparticles (LNPs) have shown promising performance in mRNA delivery. Nevertheless, a thorough understanding of the relationship between mRNA delivery efficacy and the structure of LNPs remains imperative. In this study, we systematically investigated the effects of additional hydrophobic amines on the physicochemical properties of mRNA LNPs and their delivery efficacy. The results indicated that this influence depended on the chemical structure of the additional amines and the structure of the lipid carriers. The appropriate addition of the hydrophobic amine 2C8 to lipid carriers with structural 2C8 or 2C6 tails significantly increased their mRNA delivery efficiency. In contrast, the addition of hydrophobic amine C18 to LNPs resulted in a decrease in mRNA delivery efficiency, while the addition of hydrophobic amines 2C6 and C8, as well as alkanes C12' and C16', had relatively little effect on mRNA delivery. Further investigations demonstrated that the appropriate addition of 2C8 could reduce LNP size, moderate internal hydrophobicity and LNP stability, facilitate mRNA release, enhance cellular uptake, and improve intracellular transportation of LNPs, thereby achieving superior mRNA delivery efficiency. These findings highlight the important role of additional hydrophobic amines in mRNA delivery with LNPs and provide valuable insights for the advancement of mRNA delivery carriers.
研究领域:
分子生物学
·
药物递送系统
·
生物医学工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Frontiers in Pharmacology
·
2025
·
IF 4.8
Yu Deng,Ruobing Fu,Yaqi Shang,Mengting Hu,Xirui Xin,Yubo Hou,Weixian Yu,Xinchan Liu
Introduction: Periodontitis is a chronic inflammatory disease closely associated with mitochondrial dysfunction. Uncoupling protein 2 (UCP2), located in the inner membrane of mitochondria, reduces mitochondrial membrane potential (MMP) and adenosine triphosphate (ATP) synthesis by promoting proton leakage across the membrane. This leads to decreased energy metabolism efficiency, impairing cellular glucose uptake, and disrupting intracellular energy balance. Genipin (GP), a recognized UCP2 inhibitor, exhibits anti-inflammatory and antioxidant properties. This study aimed to investigate the specific role of GP in periodontal tissue redox signaling and the potential mechanism of UCP2 in the development of periodontitis.Methods: In this study, we constructed a model of H2O2-induced oxidative stress in human periodontal ligament cells (hPDLCs). In vivo, a rat periodontitis model was established to evaluate the effects and mechanisms of GP in alleviating oxidative damage in periodontal tissues and cells.Results: Cell experiments showed that GP effectively alleviated H2O2-induced mitochondrial dysfunction and oxidative damage in hPDLCs by inhibiting UCP2 expression and function, restoring cell viability, and reducing cell apoptosis. Additionally, GP intervention increased the expression of glucose transporter 4 (GLUT4), thereby promoting cellular glucose uptake. The results of animal experiments demonstrated that GP intervention reduced alveolar bone resorption and periodontal tissue destruction in rats with periodontitis, inhibited osteoclast differentiation, improved mitochondrial dysfunction in periodontal tissue, promoted GLUT4 expression, and reduced oxidative stress levels and cell apoptosis.Discussion: GP regulates oxidative damage in periodontal tissues by maintaining mitochondrial homeostasis, promoting glucose transporter expression, and enhancing glucose uptake, with UCP2 playing a central role.
研究领域:
口腔医学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF MEDICINAL CHEMISTRY
·
2024
·
IF 6.8
Zuojie Li,Xiaojiang Duan,Peiwen Han,Guangxing Yin,Yuhao Jiang,Qing Ruan,Junbo Zhang
The development of novel tracers targeting prostate-specific membrane antigen (PSMA) has great potential for improving the diagnosis and treatment of prostate cancer (PCa). This study aimed to improve the absolute tumor uptake and tumor-to-background ratios (TBRs) of this novel PSMA tracer by increasing the number of pharmacophores, Glu-urea-Lys (EuK), that specifically bind to PSMA. We successfully synthesized four radioligands and prepared a total of 12 stable radiotracers by coordinating 99mTc with various coligands. [99mTc]Tc-EUKD-EDDA showed the best pharmacokinetic properties both in vitro and in vivo. It effectively increased the absolute uptake in tumors and resulted in good tumor retention. Rapid clearance in nontarget organs resulted in high TBRs. High-contrast SPECT/CT images were obtained within 2–6 h after injection, suggesting that [99mTc]Tc-EUKD-EDDA has great application potential in time-lapse imaging of PCa, which is important for improving the diagnostic accuracy of PCa in clinical practice.
研究领域:
医学影像学
·
核医学
·
肿瘤学
✓ 已验证
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）