MICROCHIMICA ACTA
·
2020
·Vol. 187
·期 10
·1-10
·
IF 6.232
Yao Jianmei,Zhang Lingxue,Ran Jinfeng,Wang Shasha,Dong Nan
Molecularly imprinted stir-bar coatings were created based on a hydroxylcucurbit[7]uril–paraquat inclusion complex. The inclusion complex that contained paraquat (PQ) as a template and monohydroxylcucurbit[7]uril ((OH)Q[7]) as a monomer was preassembled mainly through cavity inclusion interaction of (OH)Q[7] to form a one-dimensional self-assembly structure. The inclusion complex was anchored chemically on the surface of a glass stir bar with hydroxy-terminated poly(dimethylsiloxane) by the sol–gel technique to obtain a molecularly imprinted polymer-coated stir bar (MIP-SB). The molecularly imprinted coating showed specific adsorption for cationic PQ in aqueous media. Other quaternary amine compounds with a similar structure that coexisted in the solution, such as ethyl-viologen, diquat, and difenzoquat, were almost not extracted by the prepared MIP-SB. The sorptive capacity of the MIP-SB for PQ was nearly four times that of the non-imprinted stir bar (NIP-SB). The recognition mechanism indicated that the selectivity and extraction capacity resulted mainly from the imprinted cavity in the polymer that was formed by a one-dimensional assembly structure consisting of the (OH)Q[7]–PQ inclusion complex. The imprinted cavity was complementary to the PQ in shape, size, and functionality. A method to determine PQ in environmental water and vegetable samples was developed by combining MIP-SB sorptive extraction with HPLC-UV. The linear range was from 100 to 10,000 ng L −1 with a 8.2 ng L −1 detection limit for water samples and 0.02–0.85 mg kg −1 with a 0.005 mg kg −1 detection limit for vegetable samples. The limit of detection for both samples was lower than the EU-established maximum residual levels and that of other previously reported methods. The average recoveries were 70.0–96.1% with a relative standard deviation ≤ 7.6%, which showed the successful application in real sample analysis.
Molecularly imprinted stir-bar coatings were created based on a hydroxylcucurbit[7]uril–paraquat (PQ) inclusion complex, which showed a specific recognition toward cationic PQ. A method to determine PQ in environmental water and vegetable samples was established by combining MIP-SB sorptive extraction with HPLC-UV.
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Journal of Neuroinflammation
·
2025
·Vol. 22
·期 1
·1-19
·
IF 10.1
Chi Zhexi,Lu Bo,Liu Rongjun,Pan Chen,Meng Bo,Xing Xiuzhong,Yuan Hui,Wu Xuewei,Chen Yushan,Ren Yuxuan,Wu Wenwei,Miao Mengmeng,Chen Junping,Chen Xiaowei
Neuropathic pain, a debilitating nerve injury-induced condition, remains a significant clinical challenge. This study evaluates the effect of histone deacetylase 6 (HDAC6) inhibition in a spared nerve injury (SNI) mouse model. Systemic administration of the selective HDAC6 inhibitor ACY-1215 (20 mg/kg/day, 14 days), alleviated SNI-induced pain in mice of both sexes. ACY-1215 increased acetylated signal transducer and activator of transcription 3 (Ac-STAT3) and reduced phosphorylated STAT3 (p-STAT3) in the lumbar spinal cord of SNI mice. HDAC6 and p-STAT3 were expressed in spinal dorsal horn neurons, and SNI-enhanced HDAC6/STAT3 interaction was reversed by ACY-1215. Neuronal STAT3 overexpression induced pain hypersensitivity and elevated p-STAT3, tumor necrosis factor-alpha (TNF-α) and interleukin-1 beta (IL-1β), effects suppressed by ACY-1215. Cytokine profiling identified CC-chemokine ligand 7 (CCL7) as a key downstream effector of the HDAC6/STAT3 axis, with ACY-1215 attenuating SNI-induced CCL7 upregulation. HDAC6 knockdown in neurons reduced p-STAT3, while HDAC6 or STAT3 knockdown diminished CCL7 production. These findings demonstrate that ACY-1215 mitigates neuropathic pain by modulating STAT3 acetylation/phosphorylation and suppressing HDAC6/STAT3-driven CCL7 and cytokine release. This study underscores the role of the HDAC6/STAT3/CCL7 signaling axis in neuropathic pain and highlights the therapeutic potential of HDAC6 inhibitors for pain management.
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MOLECULAR PHARMACEUTICS
·
2020
·
IF 4.321
Lan Cui,Xiayi Feng,Wentao Liu,Hao Liu,Qian Qin,Shuangxia Wu,Suqin He,Xinchang Pang,Dong Men,Chengshen Zhu
The surface charge of nanocarriers inevitably affects drug delivery efficiency; however, the cancer cell specificity, anti-inflammatory effects, and charge-reversal points remain to be further addressed in biomedical applications. The aim of this study was to comprehensively assess the cancer cell specificity of DOX-loaded mesoporous silica-chitosan oligosaccharide-carboxymethyl chitosan nanoparticles (DOX@MSNs-COS-CMC) in MCF-7 and HeLa cells, inhibit the production of inflammatory cytokines, and improve the drug accumulation in the tumor site. Intracellular results reveal that the retention time prolonged to 48 h in both HeLa and MCF-7 cells at pH 7.4. However, DOX@MSNs-COS-CMC exhibited a cell type-dependent cytotoxicity and enhanced intracellular uptake in HeLa cells at pH 6.5, due to the clathrin-mediated endocytosis and macropinocytosis in HeLa cells in comparison with the vesicular transport in MCF-7 cells. Moreover, Pearson’s correlation coefficient value significantly decreased to 0.25 after 8 h, prompting endosomal escape and drug delivery into the HeLa nucleus. After the treatment of MSNs-COS-CMC at 200 μg/mL, the inflammatory cytokines IL-6 and TNF-α level decreased by 70% and 80%, respectively. Tumor inhibition of DOX@MSNs-COS-CMC was 0.4 times higher than free DOX, alleviating cardiotoxicity and inflammation in the HeLa xenograft tumor model. Charge-reversible DOX@MSNs-COS-CMC could be a possible candidate for clinical therapy of cervical carcinoma.
研究领域:
药理学
·
肿瘤学
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生物医学工程
·
纳米技术
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高影响因子
MOLECULES
·
2021
·Vol. 26
·期 22
·6807
·
IF 4.412
Huilan Tang,Ningyi Qin,Chang Rao,Jiahui Zhu,Haiqiang Wang,Guang Hu
Background: Danshen (DS), the dry root ofSalvia miltiorrhizaBge., has been used in traditional Chinese medicine (TCM) for many years to promote blood circulation and to inhibit thrombosis. However, the active ingredients responsible for the anti-thrombotic effect and the underlying mechanisms are yet to be fully elucidated. Methods: Molecular docking was used to predict the active ingredients in DS and their potential targets by calculating the scores of docking between DS ingredients and thrombosis-related proteins. Then, a chemical-induced zebrafish thrombosis model was applied to confirm their anti-thrombotic effects. Result: The molecular docking results indicated that compared to the control ligand, higher docking scores were observed for several compounds in DS, among which salvianolic acid B (SAB), lithospermic acid (LA), rosmarinic acid (MA), and luteolin-7-O-β-d-glucoside (LG) could attenuate zebrafish caudal vein thrombosis and recover the decrease in heart red blood cells (RBCs) in a dose-dependent manner. Conclusions: Our study showed that it is possible to screen the potential active components in natural products by combining the molecular docking method and zebrafish in vivo model.Keywords:zebrafish;molecular docking;salvianolic acid B;rosmarinic acid;lithospermic acid;luteolin-7-O-β-d-glucoside;anti-thrombotic effects
研究领域:
药理学
·
分子生物学
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中医药
·
血栓研究
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PLoS One
·
2013
·Vol. 8
·期 9
·e76544
·
IF 3.73
Qiaofeng Jin,Zhiyong Wang,Fei Yan,Zhiting Deng,Fei Ni,Junru Wu,Robin Shandas,Xin Liu,Hairong Zheng
A novel cationic microbubble (MB) for improvement of the DNA loading capacity and the ultrasound-mediated gene delivery efficiency has been developed; it has been prepared with commercial lipids and a stearic acid modified polyethylenimine 600 (Stearic-PEI600) polymer synthesized via acylation reaction of branched PEI600 and stearic acid mediated by N, N'-carbonyldiimidazole (CDI). The MBs’ concentration, size distribution, stability and zeta potential (ζ-potential) were measured and the DNA loading capacity was examined as a function of the amount of Stearic-PEI600. The gene transfection efficiency and cytotoxicity were also examined using breast cancer MCF-7 cells via the reporter plasmid pCMV-Luc, encoding the firefly luciferase gene. The results showed that the Stearic-PEI600 polymer caused a significant increase in magnitude of ζ-potential of MBs. The addition of DNA into cationic MBs can shift ζ-potentials from positive to negative values. The DNA loading capacity of the MBs grew linearly from (5±0.2) ×10 −3 pg/µm 2 to (20±1.8) ×10 −3 pg/µm 2 when Stearic-PEI600 was increased from 5 mol% to 30 mol%. Transfection of MCF-7 cells using 5% PEI600 MBs plus ultrasound exposure yielded 5.76±2.58×10 3 p/s/cm 2 /sr average radiance intensity, was 8.97- and 7.53-fold higher than those treated with plain MBs plus ultrasound (6.41±5.82) ×10 2 p/s/cm 2 /sr, (P<0.01) and PEI600 MBs without ultrasound (7.65±6.18) ×10 2 p/s/cm 2 /sr, (P<0.01), respectively. However, the PEI600 MBs showed slightly higher cytotoxicity than plain MBs. The cells treated with PEI600-MBs and plain MBs plus ultrasound showed 59.5±6.1% and 71.4±7.1% cell viability, respectively. In conclusion, our study demonstrated that the novel cationic MBs were able to increase DNA loading capacity and gene transfection efficiency and could be potentially applied in targeted gene delivery and therapy.
研究领域:
生物医学工程
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基因治疗
·
超声技术
·
癌症研究
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CHEMISTRY OF NATURAL COMPOUNDS
·
2025
·
IF 0.9
Wang Yong,Wang Wei,Liu Li-Na,Wei Dong-Lin,Liu Cong-Jun,Wei Shang-Hua,Gao Song,Yu Shu-Ping,Yao Ning,Wang Yu-Fei
A series of abietic acid derivatives modified with a triazole moiety at the C-18 position were synthesized using Huisgen 1,3-dipolar cycloaddition reaction of 18-azidoabietane with alkynes. The antitumor activity of the synthesized compounds was investigated through human cervical cancer cells (HeLa), human breast cancer cells (MCF-7) and human renal epithelial cells (HEK-293T). The outcome indicated that compounds 5e , 5f , 5j exhibited positive inhibitory activity against the tested tumor cell lines. In particular, the IC 50 value for the inhibitory activity of compound 5e against human breast cancer cells (MCF-7) was 11.2 μmol/L.
研究领域:
药物化学
·
有机合成
·
肿瘤药理学
·
天然产物衍生物
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Journal of Traditional Chinese Medicine
·
2026
·Vol. 46
·期 3
·594
·
IF 2.6
Feng HAO,Jiajia SANG,Chuanyu PENG,Jun HU,Zijian WU,Ling HU,Yihuang GU
OBJECTIVE: To investigate the effects of moxibustion at Zusanli (ST36) on ferroptosis-related proteins in synovial inflammation of rats with rheumatoid arthritis (RA) and verify the mechanism by cell experiments. METHODS: A RA rat model was established using a "disease-syndrome integration" modeling method. The rats were randomly divided into a blank control group (Control group) and a model replication group. Rats with successfully replicated RA models were further divided into a model control group (RA group) and a moxibustion treatment group (RA + Mox group). After intervention, the rats' ankle swelling degree and small animal ultrasound examination were conducted and synovial tissue was examined for pathology, lipid reactive oxygen species (ROS) detection, ferrous ion Fe 2+ double staining, and immunohistochemistry analysis. Serum from three groups of rats were extracted and used for cellular assays, cell counting kit-8 and Western blot validation. RESULTS: (a) Compared to Control group rats, RA rats showed significantly increased footpad swelling ( P < 0.01) and joint inflammation levels ( P < 0.001); compared to RA group, the RA + Mox rats showed significantly decreased footpad swelling ( P < 0.05) and joint inflammation levels ( P < 0.01). (b) There was no difference in lipid ROS levels in the synovial tissue of RA rats compared to Control group rats ( P > 0.05), but the lipid ROS levels in the synovial tissue of RA + Mox rats were significantly increased ( P < 0.01). Compared to Control group rats, RA rats had significantly lower Fe 2+ levels ( P < 0.05); compared to RA rats, the Fe 2+ levels in RA+Mox rats were significantly increased ( P < 0.01). There was no significant difference in beclin 1(BECN1) expression in the synovial tissue of RA rats compared to Control group rats ( P > 0.05), but BECN1 expression in the synovial tissue of RA + Mox rats was significantly increased ( P < 0.01) compared to RA rats. Compared to Control group rats, RA rats had significantly higher Solute Carrier Family 7 Member 11 Gene (SLC7A11) levels in synovial tissue ( P < 0.05); compared to RA rats, the SLC7A11 levels in RA + Mox rats were significantly decreased ( P < 0.05). (c) In the lipopolysaccharides (10 ng/mL) model, 50% concentration of RA rats serum promoted human RA fibroblast-like synovial cell line (MH7A) proliferation (48 h) ( P < 0.05) and 50% concentration of RA + Mox rat serum inhibited MH7A proliferation (48, 72 h) ( P < 0.001). Both 25% and 50% concentrations of RA + Mox rat serum upregulated BECN1 and downregulated SLC7A11 expression in MH7A. CONCLUSION: Moxibustion at Zusanli (ST36) suggests a potential to relieve footpad swelling and synovial inflammation in RA rats, alleviate synovial tissue hyperplasia and thickening. It may induce lipid ROS accumulation in synovial tissue, upregulating Fe 2+ levels, upregulating BECN1 expression, and downregulating SLC7A11 expression in RA rats. Moreover, 50% concentration of rat serum after moxibustion inhibited the proliferation of synovial fibroblasts and regulated the expression of ferroptosis-related proteins.
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BIOORGANIC CHEMISTRY
·
2023
·
IF 5.1
Zean Zhao,Jian Luo,Hui Liao,Fengxin Zheng,Xinhua Chen,Jiajun Luo,Yongjun Chen,Kunlu Zhao,Shuqin Zhang,Jinhong Tian,Ting Wu,Yongmei Li,Lu Li,Yang Yang,Cuiting Lin,Qun Zhang,Yuanxin Tian,Jianxin Pang
Previously we discovered a novel natural scaffold compound, isobavachin (4′, 7-dihydroxy-8-prenylflavanone), as a potent URAT1 inhibitor by shape and structure based on a virtue screening approach. In this study, further urate-lowering mechanism, pharmacokinetics and toxicities of isobavachin were conducted. Isobavachin inhibited URAT1 with an IC 50 value of 0.24 ± 0.06 μM, and residues S35, F365, I481 and R477 of URAT1 contributed to high affinity for isobavachin. Isobavachin also inhibited glucose transporter 9 (GLUT9), another pivotal urate reabsorption transporter, with an IC 50 value of 1.12 ± 0.26 μM. Molecular docking and MMGBSA results indicated that isobavachin might compete residues R171, L75 and N333 with uric acid, which leads to inhibition of uric acid transport of GLUT9. Isobavachin weakly inhibited urate secretion transporters OAT1 with an IC 50 value of 4.38 ± 1.27 μM, OAT3 with an IC 50 of 3.64 ± 0.62 μM, and ABCG2 with an IC 50 of 10.45 ± 2.17 μM. Isobavachin also inhibited xanthine oxidase (XOD) activity in vitro with an IC 50 value of 14.43 ± 3.56 μM, and inhibited the hepatic XOD activities at 5–20 mg/kg in vivo . Docking and MMGBSA analysis indicated that isobavachin might bind to the Mo-Pt catalyze center of XOD, which leads to inhibition of uric acid production. In vivo , isobavachin exhibited powerful urate-lowering and uricosuric effects at 5–20 mg/kg compared with the positive drugs morin (20 mg/kg) and RDEA3170 (10 mg/kg). Safety assessments revealed that isobavachin was safe and had no obvious toxicities. Isobavachin has little cell toxicity in HK2 cells as indicated by the MTT assay. In vivo, after treatment with 50 mg/kg isobavachin for 14 days, isobavachin had little renal toxicity, as revealed by serum CR/BUN levels, and no hepatotoxicity as revealed by ALT/AST levels. Further HE examination also suggests that isobavachin has no obvious kidney/liver damage. A pharmacokinetic study in SD rats indicated isobavachin had lower bioavailability (12.84 ± 5.13 %) but long half-time (7.04 ± 2.68 h) to maintain a continuous plasma concentration. Collectively, these results indicate that isobavachin deserves further investigation as a candidate anti-hyperuricemic drug with a novel mechanism of action: selective urate reabsorption inhibitor (URAT1/GLUT9) with a moderate inhibitory effect on XOD.
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NAUNYN-SCHMIEDEBERGS ARCHIVES OF PHARMACOLOGY
·
2022
·Vol. 395
·期 10
·1283-1295
·
IF 3.195
Xiong Ziwei,Cui Yushun,Wu Jiahui,Shi Lingyu,Quan Wen,Yang Shilin,Feng Yulin
Pteris cretica L. var. nervosa is one of the most well-known Chinese medicines. Although it is widely used to treat jaundice hepatitis, the main ingredient for its treatment was not thoroughly explored until recently. Essentially, the purpose of this study is to find the monomer compound in Pteris cretica L. var. nervosa , which is most likely to be effective in treating liver injury. Through the model of LPS/D-gal-induced liver injury in mice, the best therapeutic site of the total extract was explored, the chemical components of the parts with the best therapeutic effect were separated, a total of 10 flavonoids were isolated, and the RAW264.7 cells induced by LPS were used as the experimental model to explore the preliminary anti-inflammatory activity of NO production in vitro. Finally, the anti-inflammatory activity and the highest content in this plant Luteolin-7-O-rutinoside (LUT) were selected, as the object of study in vivo. It was found that LUT could not only reduce alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels, but also significantly reduce the release of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and interleukin-1β (IL-1β), and inhibit PI3K/AKT/AMPK/NF-κB pathway. In addition, LUT can increase levels of SOD and GSH to reduce oxidative stress. It has an obvious therapeutic effect on acute liver injury induced by LPS/D-gal in mice. Therefore, infer LUT is a functional substance in Pteris cretica L. var. nervosa. Graphical abstract
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JOURNAL OF SEPARATION SCIENCE
·
2020
·Vol. 43
·期 12
·2290-2300
·
IF 2.878
Guanghui Ren,Huili Chen,Mei Zhang,Nan Yang,Hui Yang,Chuanru Xu,Jiaming Li,Chen Ning,Zhongjin Song,Shiyu Zhou,Siliang Zhang,Xiaoqian Wang,Yang Lu,Ning Li,Yongjie Zhang,Xijing Chen,Di Zhao
Oroxylin A, obtained from the root of Scutellaria baicalensis Georgi , is a flavonoid with antitumor and other pharmacological activities. Our previous studies showed for the first time that it is mainly metabolized to oroxylin A sodium sulfonate by sulfotransferase enzymes in beagle dogs. In this study, rapid, universal, selective, and robust ultra-high-performance liquid chromatography–tandem mass spectrometry methods were established and fully validated to quantitatively detect oroxylin A, oroxylin A 7-O-glucuronide, and oroxylin A sodium sulfonate in beagle dog plasma. The quantitative analysis for oroxylin A sodium sulfonate was reported for the first time. Plasma samples were processed with acetonitrile, a universal protein precipitant. Gradient elution was performed to resolve carryover effects and to achieve separation efficiency and sufficient chromatographic retention. The linear relationships of oroxylin A, oroxylin A 7-O-glucuronide, and oroxylin A sodium sulfonate in plasma were in the range of 2.0–500.0, 5.0–500.0, and 1.881–940.5 ng/mL, respectively. The assay method was successfully applied to pharmacokinetic study. This is the first paper that reveals the pharmacokinetic profile of oroxylin A, oroxylin A 7-O-glucuronide, and oroxylin A sodium sulfonate after single-dose intravenous and oral administration of Oroxylin A in beagle dogs.
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International Journal of Nanomedicine
·
2018
·
IF 4.37
Li Xu,Jing Du,Caifeng Wan,Yu Zhang,Shaowei Xie,Hongli Li,Hong Yang,Fenghua Li
Background The development of nanoscale molecularly targeted ultrasound contrast agents (UCAs) with high affinity and specificity is critical for ultrasound molecular imaging in the early detection of breast cancer. Purpose To prospectively evaluate ultrasound molecular imaging with dual-targeted gold nanoshelled poly(lactide-co-glycolic acid) nanocapsules carrying vascular endothelial growth factor receptor type 2 (VEGFR2) and p53 antibodies (DNCs) in MCF-7 orthotopic mice model. Methods DNCs were fabricated with an inner PLGA and outer gold nanoshell spherical structure. Its targeting capabilities were evaluated by confocal laser scanning microscopy (CLSM) and flow cytometry (FCM) in vitro. Contrast-enhanced ultrasound imaging (CEUS) with DNCs was evaluated qualitatively and quantitatively in vitro and in MCF-7 orthotopic mice model by two different systems. The biodistribution of NCs in mice was preliminary investigated. Differences were calculated by using analysis of variance. Results DNCs showed a well-defined spherical morphology with an average diameter of 276.90±110.50 nm. In vitro, DNCs exhibited high target specificities (79.01±5.63% vs. 2.11±1.07%, P <0.01; 75.54±6.58% vs. 5.21±3.12%, P <0.01) in VEGFR2- and p53-positive cells compared with control cells. In vivo, CEUS displayed a significantly higher video intensity in two systems using DNCs in comparison with non-targeted PLGA@Au NCs and single-targeted NCs. Biodistribution studies revealed that more DNCs in breast cancer tissue could be detected in mice than in other NCs ( P <0.05). Conclusion DNCs were demonstrated to be novel dual-targeted UCAs and may have potential applications in early non-invasive visualization of breast cancer.
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Acta Biomaterialia
·
2018
·
IF 6.383
Yun Wang,Feihu Wang,Ying Liu,Shaohui Xu,Yuanyuan Shen,Nianping Feng,Shengrong Guo
Effects of nanosized drug delivery systems on cancer are often compromised due to their low drug loadings, premature drug release and multi-drug resistance (MDR). Herein, we reported a glutathione detonated and pH responsive nano-cluster of Au nanorods (AuNRs) with chemotherapeutic doxorubicin (DOX) and pre-chemosensitizer polycurcumin to treat MCF-7/ADR cells. The nano-cluster was prepared by self-assembling of AuNRs conjugated with DOX and amphiphilic poly(curcumin-co-dithiodipropionic acid)-b-biotinylated poly(ethylene glycol) via an emulsion/solvent evaporation technique, termed AuNR Cluster. The AuNR Cluster had a high drug loading (31.5% DOX), presenting much better aqueous solubility and stability at physiological pH than their individual AuNRs. The AuNR Cluster could be detonated to be their individual AuNRs at an intracellular concentration level of glutathione (GSH) (5 mM) and triggered to release DOX at an acidic pH (pH 6.8 or 5.0), which effectively facilitated cellular uptake of DOX (607 vs 356 a.u. for AuNRs at 12 h) and inhibited DOX efflux (471.33 vs 39.17 a.u. for free DOX at 24 h). The IC 50 value of DOX against MCF-7/ADR cells for AuNR Cluster was 4.15 µg/mL, much lower than that for free DOX (90.97 µg/mL). The AuNR Cluster took much more photothermal effects than their corresponding AuNRs and presented enhanced anti-tumor effect (IC 50 : 2.61 µg/mL) under 808 nm laser irradiation. Statement of Significance Nano-sized drug delivery systems for anti-MDR cancer is still a challenging task. Herein, AuNR Cluster was self-assembled by individual AuNRs via emulsion/solvent evaporation technique, having a structure consisting of hydrophobic DOX/PCDA-AuNR core and hydrophilic biotin-PEG chain shell. AuNR Cluster is detonated to disintegrate and yield its individual AuNRs at an intracellular concentration level of glutathione (5 mM) and triggered to release DOX at an acidic pH (6.8 or 5.0). In comparison with its individual AuNRs, AuNR Cluster has better water solubility and stability, greater photothermal effects under NIR irradiation, bigger cytotoxicity against MCF-7/ADR cells. AuNR Cluster is expected to be a potential nanomedicine for treatment of MDR cancer.
研究领域:
纳米医学
·
癌症研究
·
药物递送系统
·
材料科学
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