Biomaterials Science
·
2018
·Vol. 6
·期 8
·2172-2188
·
IF 5.831
Haifeng Sun,Dinglingge Cao,Yanhong Liu,Hui Wang,Xue Ke,Tianyuan Ci
Tumor metastasis has become a major obstacle for the clinical treatment of malignant breast cancer. Thus, a delivery system capable of both antitumor and anti-metastasis efficacy is desired. In this work, a low molecular weight heparin (LMWH)-based reduction-sensitive delivery system was developed, aiming to combine the properties of both the antitumor drug and active excipients to achieve a synergistic antitumor and anti-metastatic efficiency as well as resolving the potential adverse effects of both doxorubicin and LMWH. That is, the efficiency of DOX could be enhanced and its toxicity could be lowered. Meanwhile, the biological properties of LMWH could be strengthened and its bleeding risk could also be alleviated. Briefly, drug-loaded crosslinked nanoparticles (DOX/cLLHC2) had a longer blood circulation time and exhibited a rapid reduction-triggered release of DOX. The in vitro assays revealed that DOX/cLLHC2 exhibited a higher cellular uptake and cytotoxicity compared to free DOX. Meanwhile, for the existence of LMWH, DOX/cLLHC2 inhibited cell migration and invasion, as well as effectively inhibited the tube-like formation of human umbilical vein endothelial cells. DOX/cLLHC2 possessed a superior tumor accumulation compared to lipoic acid unmodified nanoparticles and free DOX. Also, DOX/cLLHC2 exhibited encouraging antitumor and anti-metastasis efficiency in an orthotopic breast cancer model. Overall, DOX/cLLHC2 could exert antitumor, anti-metastasis, and anti-angiogenesis efficacy simultaneously as well as having lower systemic toxicity, which makes it suitable for the therapy of metastatic breast carcinoma.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ANALYTICAL AND BIOANALYTICAL CHEMISTRY
·
2018
·Vol. 410
·期 20
·4805-4813
·
IF 3.307
Wang Yanying,Liu Yaqin,Ding Fang,Zhu Xiaoyan,Yang Li,Zou Ping,Rao Hanbing,Zhao Qingbiao,Wang Xianxiang
In this study, we developed a simple colorimetric approach to detect glutathione (GSH). The proposed approach is based on the ability of CuS-PDA-Au composite material to catalytically oxidize 3,3′,5,5′-tetramethylbenzidine (TMB) to ox-TMB to induce a blue color with an absorption peak centered at 652 nm. However, the introduction of GSH can result in a decrease in oxidized TMB; similarly, it can combine with Au nanoparticles (Au NPs) on the surface of CuS-PDA-Au composite material. Both approaches can result in a fading blue color and a reduction of the absorbance at 652 nm. Based on this above, we proposed a technique to detect GSH quantitatively and qualitatively through UV-Vis spectroscopy and naked eye, respectively. This approach demonstrates a low detection limit of 0.42 μM with a broad detection range of 5 × 10 −7 –1 × 10 −4 M with the assistance of UV-Vis spectroscopy. More importantly, this approach is convenient and rapid. This method was successfully applied to GSH detection in human serum and cell lines.
A colorimetric approach has been developed by exploiting the peroxidase-like activity of CuS-polydopamine-Au composite for sensitive glutathione detection.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Royal Society Open Science
·
2018
·Vol. 5
·期 3
·
IF 2.504
Chang Shu,Tengfei Li,Wen Yang,Duo Li,Shunli Ji,Li Ding
The present work is focused on the design and development of novel amphotericin B (AmB)-conjugated biocompatible and biodegradable polypeptide hydrogels to improve the antifungal activity. Using three kinds of promoting self-assembly groups (2-naphthalene acetic acid (Nap), naproxen (Npx) and dexamethasone (Dex)) and polypeptide sequence (Phe-Phe-Asp-Lys-Tyr, FFDKY), we successfully synthesized the Nap-FFDK(AmB)Y gels, Npx-FFDK(AmB)Y gels and Dex-FFDK(AmB)Y gels. The AmB-conjugated hydrogelators are highly soluble in different aqueous solutions. The cryo-transmission electron microscopy and scanning electron microscopy micrographs of hydrogels afford nanofibres with a width of 20–50 nm. Powder X-ray diffraction analyses demonstrate that the crystalline structures of the AmB and Dex are changed into amorphous structures after the formation of hydrogels. Circular dichroism spectra of the solution of blank carriers and the corresponding drug deliveries further help elucidate the molecular arrangement in gel phase, indicating the existence of turn features. The in vitro drug releases suggest that the AmB-conjugated hydrogels are suitable as drug-controlled release vehicles for hydrophobic drugs. The antifungal effect of AmB-conjugated hydrogels significantly exhibits the antifungal activity against Candida albicans. The results of the present study indicated that the AmB-conjugated hydrogels are suitable carriers for poorly water soluble drugs and for enhancement of therapeutic efficacy of antifungal drugs.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Scientific Reports
·
2018
·Vol. 8
·期 1
·1-18
·
IF 4.122
Du Jing,Li Xiao-Yu,Hu He,Xu Li,Yang Shi-Ping,Li Feng-Hua
Molecularly-targeted contrast enhanced ultrasound (US) imaging is a promising imaging strategy with large potential for improving diagnostic accuracy of conventional US imaging in breast cancer detection. Therefore, we constructed a novel dual-targeted nanosized US contrast agent (UCA) directed at both vascular endothelial growth factor receptor 2 (VEGFR2) and human epidermal growth factor receptor 2 (HER2) based on perfluoropropane (C 3 F 8 )-filled poly(lactic-co-glycolic acid) (PLGA) (NBs) for breast cancer detection. In vitro , single- or dual-targeted PLGA NBs showed high target specificities and better effects of target enhancement in VEGFR2 or HER2-positive cells. In vivo , US imaging signal in the murine breast cancer model was significantly higher ( P < 0.01) for dual-targeted NBs than single-targeted and non-targeted NBs. Small animal fluorescence imaging further confirmed the special affinity of the dual-targeted nanosized contrast agent to both VEGFR2 and HER2. Immunofluorescence and immunohistochemistry staining confirmed the expressions of VEGFR2 and HER2 on tumor neovasculature and tumor cells of breast cancer. In conclusions, the feasibility of using dual-targeted PLGA NBs to enhance ultrasonic images is demonstrated in vitro and in vivo . This may be a promising approach to target biomarkers of breast cancer for two site-specific US molecular imaging.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Journal of Materials Chemistry B
·
2018
·Vol. 6
·期 19
·3128-3135
·
IF 4.776
Wenhao Zhou,Ling Lu,Dafu Chen,Zhengao Wang,Jinxia Zhai,Renxian Wang,Guoxing Tan,Jianping Mao,Peng Yu,Chengyun Ning
Conductive polymers (CPs) are frequently used as neural and osteogenic implants for signal recording and electrical stimulation due to their electroactive and good biocompatibility. However, these implants often fail due to bacterial infection. In this research, a novel nano-functionalized polypyrrole (PPy) with high surface potential was electrochemically developed to improve the antibacterial properties of CPs. Sulfosalicylic acid (SSA)—a biomolecule with abundant negatively charged functional groups—was introduced to not only successfully assist in the electrical assembly of Py micelles into a bacterial extracellular matrix mimetic nanostructure, but also to modulate the surface electrical properties of PPy. Scanning Kelvin probe microscopy (SKPM) results confirm the increased positive charges on SSA-assisted PPy (PPy/SSA nanorod and irregular PPy/SSA film) relative to the irregular PPy/Cl film. Plate colony-counting experiments confirm that SSA-assisted PPy has excellent antibacterial properties relative to the irregular PPy/Cl film. The higher antibacterial rate for PPy/SSA nanorods suggests a synergistic effect via the nanorod structure and the high surface potential induced by dopants. Cytotoxicity testing demonstrates that PPy/SSA samples were nontoxic to the cells. Our work provides an effective way to develop antibacterial CPs.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ACS Applied Materials & Interfaces
·
2018
·
IF 8.097
Dandan Jiang,Weiwei Mu,Xiuping Pang,Yongjun Liu,Na Zhang,Yunmei Song,Sanjay Garg
Enhancing cytosol delivery of exogenous antigens in antigen presenting cells can improve cross-presentation and CD8+ T cell-mediated immune response. The antigen cytosol delivery speed, which has great importance on the rate of MHC class I molecules (MHC I) antigen presentation pathway and cytotoxic T lymphocytes (CTLs) induction, has not been well studied. We hypothesized that micelle-tailored vaccine with multiple cascaded lysosomal responsive capabilities could accelerate lysosomal escape and enhance cancer immunotherapy. To test our hypothesis, we created a novel micellar cancer vaccine (ovalbumin-loaded pH/redox dual-sensitive micellar vaccine, OLM-D) by cleavable conjugation of an antigen with house-made amphiphilic poly(l-histidine)–poly(ethylene glycol) (PLH–PEG) in current study. OLM-D was supposed to achieve cascade cytosol delivery of ovalbumin through three steps in terms of (i) initial redox triggered ovalbumin release, (ii) promoted proton inflow and micelle disassembly, and (iii) speeded proton sponge effect and lysosome bulging/broke. Redox-sensitive antigen release and consequently accelerative OLM-D disassembly were confirmed by sodium dodecylsulphate polyacrylamide gel electrophoresis (SDS–PAGE), transmission electronic microscopy (TEM), particle sizes, zeta potentials, and in vitro Ova release evaluation. The speeded cytosol delivery of ovalbumin was visualized under a confocal laser scanning microscope (CLSM). The ability of OLM-D to increase the MHC I molecule combination rate and antigen cross-presentation efficiency was identified by antigen presentation assay and maturation assay in bone marrow-derived dendritic cells (BMDCs). In vivo, the capability of OLM-D to accumulate in draining lymph nodes (LNs) after injection was visualized by real-time near infrared fluorescence imaging (NIRF) and the distribution order in different LNs was first observed (a, d, c, b). Enhanced cancer immunity of OLM-D was confirmed by increased CD3+CD8+ T cell quantity, CD3+CD8+25D11.6+ T cells quantity, and IFN-γ, IL-2 secretion post subcutaneous or intraperitoneal injection (p < 0.05). Taken together, our results indicated that OLM-D provided a promising cascade cytosol delivery strategy, which held great potential to guide further design of nano-particulate cancer vaccines for efficient cancer immunotherapy.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
RSC Advances
·
2018
·Vol. 8
·期 5
·2459-2468
·
IF 2.936
Dan Zhang,Yun-ling Gao,Sheng Jiang,Yiwen Chen,Yi Zhang,Zheng Pan
Lamiophlomis rotata (L. rotata) is a Tibetan medicinal herb used for centuries that contains iridoid glycosides (IGs), which are pharmacologically active ingredients and can be used for quality control. The IG profiles of the underground and aerial parts of the plant were determined by UPLC-TOF-MS to evaluate the similarity and variability of the different herbal parts listed in the Chinese Pharmacopoeia. Twenty-six IGs were detected in the total ion current (TIC) profile of L. rotata, and twenty-two of these were identified by comparing the retention times and mass spectra of the compounds to those of authentic standards. Among these compounds, five IGs with the same molecular formula (C17H26O11) were identified for the first time by mass spectrometry based on their different hydroxyl group-substituted positions. The aerial part has a similar chemical profile to that of the roots. The difference between the two parts was determined by multivariate statistical analysis of the UPLC-TOF-MS data of 24 specimens. Sesamoside was explored as the most characteristic marker to distinguish the two parts of L. rotata. To further estimate the distinction between the two parts, the content of total IGs and the antioxidant capacity were investigated in samples from different locations. The aerial parts showed a high content of total IGs and high antioxidant capacity, although not higher than those of the roots. The results also suggest the dosage should be increased when the aerial parts are used as crude medicinal materials instead of the underground parts.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
SPECTROCHIMICA ACTA PART A-MOLECULAR AND BIOMOLECULAR SPECTROSCOPY
·
2018
·
IF 2.88
Chaojie Qu,Duobao Zhang,Ran Yang,Jingyu Hu,Lingbo Qu
In this work, a novel nitrogen and sulfur co-doped graphene quantum dots (N,S/GQDs) were synthesized by a simple and green pyrolysis method with citric acid as carbon source, d ‑penicillamine as doped molecule. The obtained N,S/GQDs shows good water solubility, low cytotoxicity and high quantum yield of 56.4%. The doping of N and S can efficient promoted the coordination between the residual group of N,S/GQDs and Hg 2+ , thus, the fluorescence of N,S/GQDs can be dramatically and selectively quenched by Hg 2+ . Under the optimum conditions, the quenching effect of Hg 2+ to N,S/GQDs was lined with its concentrations in the range of 0.9 to 30 nM with a detection limit of 0.69 nM. 100 fold of common metals had no influence for the determination of Hg 2+ . When Hela cells were incubated into the N,S/GQDs solutions for 2 h, more than 85% Cells still kept living even at a high concentration of 400 μg/mL suggesting the good biocompatibility and low toxicity of the obtained N,S/GQDs. Besides this, the N,S/GQDs also showed good cell permeability and could enter into the cell and showed bright blue light. Thus, they were successfully applied as a powerful fluorescent nano-sensor for imaging detection of mercury ions in the living cells.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Biomaterials Science
·
2018
·Vol. 6
·期 9
·2360-2374
·
IF 5.831
Dong Zhang,Jincheng Yang,Jibin Guan,Bin Yang,Shenwu Zhang,Mengchi Sun,Ruitao Yang,Tao Zhang,Ruoshi Zhang,Qiming Kan,Haotian Zhang,Zhonggui He,Lei Shang,Jin Sun
Prodrug self-nanoassemblies have many advantages for anticancer drug delivery, including high drug loading rate, resistance to recrystallization, and on-demand drug release. However, few studies have focused on their protein corona, which is inevitably formed after entering the blood and determines their subsequent fates in vivo. To actively tune the protein corona of prodrug nanoassemblies, three maleimide-paclitaxel prodrugs were synthesized via different redox-sensitive linkers (ester bond, thioether bond and disulfide bond). After incubation with rat plasma, the surface maleimide groups effectively captured albumins, resulting in albumin-enriched protein corona. The recruited albumin corona enabled enhanced tumor accumulation and facilitated cellular uptake, ensuring the high-efficiency delivery of nanoassemblies to tumor cells. Surprisingly, we found that the traditionally reduction-sensitive disulfide bond could also be triggered by reactive oxygen species (ROS). Such a redox dual-responsive drug release property of the disulfide bond-containing prodrug nanoassemblies further increased the selectivity in cytotoxicity between normal and tumor cells. Moreover, the disulfide bond-containing prodrug nanoassemblies exhibited the highest antitumor efficacy in vivo compared to marketed Abraxane® and other prodrug nanoassemblies. Thus, the fabrication of the maleimide-decorated disulfide bond bridged prodrug nanoassembly, integrating a tunable protein corona and on-demand drug release, is a promising strategy for improved cancer chemotherapy.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ACS Applied Materials & Interfaces
·
2019
·
IF 8.456
Shen-Zhen Ren,Dan Zhu,Xiao-Hua Zhu,Bin Wang,Yu-Shun Yang,Wen-Xue Sun,Xiao-Ming Wang,Peng-Cheng Lv,Zhong-Chang Wang,Hai-Liang Zhu
Responsive nanocarriers with biocompatibility and precise drug releasing capability have emerged as a prospective candidate for anticancer treatment. However, the challenges imposed by the complicated preparation process and limited loading capacities have seriously impeded the development of novel multifunctional drug delivery systems. Here, we developed a novel and dual-responsive nanocarrier based on a nanoscale ZIF-8 core and an organosilica shell containing disulfide bridges in its frameworks through a facile and efficient strategy. The prepared ZIF-8@DOX@organosilica nanoparticles (ZDOS NPs) exhibited a well-defined structure and excellent doxorubicin (DOX) loading capability (41.2%) with pH and redox dual-sensitive release properties. The degradation of the organosilica shell was observed after 12 h incubation with a 10 mM reducing agent. Confocal imaging and flow cytometry analysis further proved that the nanocarriers can efficiently enter cells and complete intracellular DOX release under the low pH and high glutathione concentrations, which resulted in an enhanced cytotoxicity of DOX for cancer cells. Meanwhile, subcellular localization experiments revealed that the ZDOS NPs entered cells mainly by endocytosis and then escaped from lysosomes into the cytosol. Moreover, in vivo assays also demonstrated that the ZDOS NPs exhibited negligible systemic toxicity and significantly enhanced anticancer efficiencies compared with free DOX. In summary, our prepared pH and redox dual-responsive nanocarriers provide a potential platform for controlled release and cancer treatment.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ACS Applied Materials & Interfaces
·
2019
·
IF 8.456
Jingmin Wang,Xiaolong Hu,Haizhen Ding,Xin Huang,Mingsheng Xu,Zhenzhen Li,Dong Wang,Xu Yan,Yang Lu,Yunjun Xu,Yan Chen,Paulo Cesar Morais,Yupeng Tian,Ren-Quan Zhang,Hong Bi
Commercial gadolinium-based materials have been widely used as contrast agents for magnetic resonance imaging (MRI), but the high toxicity of leaking free Gd3+ ions still raises biosafety concerns. Here, we develop a novel, safe, and efficient MRI contrast agent based on a stable Fe(III) complex of fluorine and nitrogen co-doped carbon dots (F,N-CDs) that was prepared from glucose and levofloxacin by a simple microwave-assisted thermal decomposition method. The obtained Fe3+@F,N-CD complex exhibits higher longitudinal relaxivity (r1 = 5.79 mM–1·s–1) than that of the control samples of the Fe3+@CD complex (r1 = 4.23 mM–1 s–1) and free Fe3+ (r1 = 1.59 mM–1 s–1) in aqueous solution, as assessed by a 1.5 T NMR analyzer. More importantly, the Fe3+@F,N-CD complex is very stable with a large coordination constant of 1.06 × 107 in aqueous medium. While incubated with HeLa cells, the Fe3+@F,N-CD complex shows clear MR images, demonstrating that it has potential to be an excellent MRI contrast agent. Furthermore, in vivo MRI experiments indicate that the Fe3+@F,N-CD complex provides high-resolution MRI pictures of 4T1 tumor bearing BALB/c mice 15 min after injection and can be completely excreted 2 h after administration. No cytotoxicity was observed with F,N-CDs and Fe concentration up to 0.2 mg/mL and 0.3 mM in 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide cell proliferation assay, respectively. The possible mechanism of the enhanced MRI effect of the Fe3+@F,N-CD complex is therefore proposed. The extremely low toxicity, high r1 relaxivity, strong photoluminescence, and low synthetic cost enable the Fe3+@F,N-CD complex to be a safe and promising T1-weighted MRI contrast agent for clinical applications.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
DRUG DEVELOPMENT AND INDUSTRIAL PHARMACY
·
2019
·
IF 2.367
Xin-Cheng Zhong,Wen-Hong Xu,Zi-Ting Wang,Wang-Wei Guo,Jie-Jian Chen,Ning-Ning Guo,Tian-Tian Wang,Meng-Ting Lin,Zhen-Tao Zhang,Yi-Ying Lu,Qi-Yao Yang,Min Han,Dong-Hang Xu,Jian-Qing Gao
Objective: This study was aimed to develop DOX-TPP loaded acetal-PEG-PCCL micelles to improve the clinical efficacy of drug resistance tumor.Significance: Chemotherapy is one of the main treatments for breast cancer but is plagued by multidrug resistance (MDR). DOX-TPP-loaded micelles can enhance the specific concentration of drugs in the tumor and improve the efficacy and overcome MDR.Methods: In this study, DOX-TPP-loaded micelles based on acetal-PEG-PCCL were prepared and their physicochemical properties were characterized. The cellular uptake and ability to induce apoptosis of the micelles was confirmed by flow cytometry in MCF-7/ADR cells. In addition, cytotoxicity of the micelles was studied in MCF-7 cells and MCF-7/ADR cells. Confocal is used to study the subcellular distribution of DOX. Free DOX-TPP or DOX-TPP-loaded acetal-PEG-PCCL micelles were administered via intravenous injection in the tail vain for the biodistribution study in vivo.Results: The diameter of micelles was about 102.4 nm and their drug-loading efficiency is 61.8%. The structural characterization was confirmed by 1H NMR. The micelles exhibited better antitumor efficacy compared to free doxorubicin in MCF-7/ADR cells by MTT assay. The apoptotic rate and the cellular uptake of micelles were significantly higher than free DOX and DOX-TPP. Micelles can efficiently deliver mitochondria-targeting DOX-TPP to tumor cells. The result of bio-distribution showed that the micelles had stronger tumor infiltration ability than free drugs.Conclusions: In this study, mitochondriotropic DOX-TPP was conjugated to the nanocarrier acetal-PEG-PCCL via ionic interaction to form a polymer, which spontaneously formed spherical micelles. The cytotoxicity and cellular uptake of the micelles are superior to free DOX and exhibit mitochondrial targeting and passive tumor targeting, indicating that they have potential prospects.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）