MOLECULES
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2019
·Vol. 24
·期 13
·2483
·
IF 3.06
Krishan Parashar,Siddhartha Sood,Ali Mehaidli,Colin Curran,Caleb Vegh,Christopher Nguyen,Christopher Pignanelli,Jianzhang Wu,Guang Liang,Yi Wang,Siyaram Pandey
Melanoma is the leading cause of skin-cancer related deaths in North America. Metastatic melanoma is difficult to treat and chemotherapies have limited success. Furthermore, chemotherapies lead to toxic side effects due to nonselective targeting of normal cells. Curcumin is a natural product ofCurcuma longa(turmeric) and has been shown to possess anti-cancer activity. However, due to its poor bioavailability and stability, natural curcumin is not an effective cancer treatment. We tested synthetic analogs of curcumin that are more stable. One of these derivatives, Compound A, has shown significant anti-cancer efficacy in colon, leukemia, and triple-negative inflammatory breast cancer cells. However, the effects of Compound A against melanoma cells have not been studied before. In this study, for the first time, we demonstrated the efficacy of Compound A for the selective induction of apoptosis in melanoma cells and its interaction with tamoxifen, taxol, and cisplatin. We found that Compound A induced apoptosis selectively in human melanoma cells by increasing oxidative stress. The anti-cancer activity of Compound A was enhanced when combined with tamoxifen and the combination treatment did not result in significant toxicity to noncancerous cells. Additionally, Compound A did not interact negatively with the anti-cancer activity of taxol and cisplatin. These results indicate that Compound A could be developed as a selective and effective melanoma treatment either alone or in combination with other non-toxic agents like tamoxifen.Keywords:melanoma;curcumin analog;apoptosis;oxidative stress;drug–drug interaction;tamoxifen;taxol;cisplatin
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Artificial Cells Nanomedicine and Biotechnology
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2018
·
IF 3.026
Xue Dong,Shaohua Zou,Chunjing Guo,Kaili Wang,Feng Zhao,Huaying Fan,Jungang Yin,Daquan Chen
The traditional therapy of cancer has systemic side effects, and many cancers, such as human breast cancer and lung cancer easily metastasize to bones, leading to the formation of secondary tumours. This study was aimed at enhancing the anti-tumour effect of curcumin (CUR) and preventing tumour spread to the bone. A novel multifunctional redox-responsive and CD44 receptor targeting polymer-drug, poly alendronate-hyaluronan-S-S-curcumin copolymer (ALN-oHA-S-S-CUR) based CUR and alendronate (ALN) were synthesized successfully with the disulphide bond linker. The structure of ALN-oHA-S-S-CUR was characterized by 1H-NMR. The nanomedicine had natural anti-tumour drugs (CUR) as the hydrophobic kernel, and targeting CD44 receptor oligosaccharides of hyaluronan (oHA) and other anti-tumour drugs (ALN) as hydrophilic shell, named ALN-oHA-S-S-CUR conjugates, which could self-assemble into micelle-like nano-spheres in water via a dialysis method with hydrodynamic diameters of 179 ± 23 nm. Interestingly, the cur-loaded ALN-oHA-S-S-CUR micelles were stable in PBS but were capable of releasing the drug under the reducing environment. The rate of drug release was proportional to the GSH concentration. The uptake and cytotoxicity of micelles were higher in MDA-MB-231 cells than in MCF-7 cells because of a higher expression of the CD44 receptor in the former cell line. And compared to the cur-loaded oHA-CUR micelles, the cur-loaded ALN-oHA-S-S-CUR micelles had a good cellular uptake in 2D cancer cell and penetrability in 3D cancer cell spheroids. These results indicated the active targeting redox-sensitive micelles were promising as intracellular drug delivery systems for cancer treatment.
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BIOLOGICAL & PHARMACEUTICAL BULLETIN
·
2019
·Vol. 42
·期 6
·886-891
·
IF 1.54
Yangbiao He,Xujun Lang,Dong Cheng,Zhihao Yang
Previous studies implicated the mammalian target of rapamycin (mTOR)/hypoxia-inducible factor-1α (HIF-1α)/vascular endothelial growth factor (VEGF) pathway in renal fibrosis and found that curcumin could suppress the expression of mTOR. Therefore, the aim of the present study was to investigate the therapeutic effects of curcumin against chronic renal failure (CRF) in a rat model induced by 5/6 nephrectomy through inhibition of mTOR/HIF-1α/VEGF signaling. A total of 70 male Sprague–Dawley rats were divided into seven groups: a sham group, a CRF group, and five treatment groups. Except for the sham rats, all rats underwent 5/6 nephrectomy to induce CRF. The 5/6 nephrectomized rats received treatment with curcumin vehicle, everolimus vehicle, curcumin, everolimus, or the combination of curcumin and everolimus. Everolimus, a specific inhibitor of mTOR, was used as a positive control. At the end of treatment, blood biochemical indexes, proteinuria and the kidney index were detected. Moreover, histological change was examined by hematoxylin and eosin staining, and protein expression levels were detected by Western blotting. The blood biochemical indexes, proteinuria, and kidney index were increased in the CRF group as compared to the sham group, which was accompanied by marked activation of the mTOR/HIF-1α/VEGF pathway. However, curcumin, as well as everolimus, restored or ameliorated these changes. These results indicate that activation of the mTOR/HIF-1α/VEGF signaling pathway plays an important role in the occurrence and development of CRF, and that curcumin has renoprotective effects by blocking activation of this pathway.
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INTERNATIONAL JOURNAL OF PHARMACEUTICS
·
2019
·
IF 4.213
Ruoning Wang,Jiawei Han,Ai Jiang,Rong Huang,Tingming Fu,Lingchong Wang,Qin Zheng,Wen Li,Junsong Li
Curcumin (CUR) has gained increasing interest worldwide due to multiple biological activities . However, the therapeutic application remains limited because of its low aqueous solubility, intestinal metabolism and poor membrane permeability. In present study, an excipient-free CUR solid dispersion co-formed with piperine (PIP), the absorption enhancer involving metabolism-permeability, was successfully prepared by melting and quench cooling (co-amorphous CUR-PIP). The co-amorphous CUR-PIP exhibited superior performance in non-sink dissolution compared with crystalline and amorphous CUR, and showed physically stable at least 3 months, attributing to the strong molecular interactions between CUR and PIP as evaluated by FTIR spectra. Furthermore, the combination of PIP with CUR in the co-amorphous formulation could inhibit the glucuronidation of CUR, as exhibited in the in vitro assay of rat intestinal microsomes. The co-amorphous CUR-PIP would also exhibit higher gastrointestinal membrane permeability of CUR, as confirmed by P app of CUR in Caco-2 model. After administration of co-amorphous CUR-PIP, the AUC of CUR significantly increased by 2.16- and 1.92-fold those in crystalline and amorphous CUR, respectively. This study demonstrates that the developed co-amorphous CUR-PIP can enhance the bioavailability of CUR by increasing its dissolution, inhibiting metabolic processes, and facilitating membrane permeability.
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MICROCHIMICA ACTA
·
2019
·Vol. 186
·期 10
·1-12
·
IF 5.479
Bu Lingli,Luo Tao,Peng Huanjun,Li Ling,Long Dengying,Peng Jingdong,Huang Jing
Nitrogen-doped carbon dots (N-CDs) with fluorescence excitation/emission maxima at 365/450 nm were prepared by a one-step hydrothermal approach. The dots possess remarkable photostability, fluorescence blinking and good biocompatibility, and this favors utilization in stochastic optical reconstruction microscopy (STORM). A spatial resolution down to ~60 nm was achieved when imaging HeLa cells using 647-nm laser excitation. This opens new possibilities for various super-resolution techniques based on stochastic optical switching. The remarkable optical properties of the N-CDs also enable them to be applied as invisible security ink for use in patterning, information storage and anti-counterfeiting. Further, it is found that the fluorescence of the N-CDs can be quenched by curcumin with high efficiency due to a combination of inner filter effect and static quenching. Based on this, a fluorometric assay with a detection limit of 21 ng mL −1 was developed for the determination of curcumin.
Schematic representation of the applications of N-doped carbon dots (N-CDs). Curcumin quenches the fluorescence of N-CDs with high efficiency. The remarkable optical properties of the N-CDs enable them to be applied in fluorescent ink, cell imaging and stochastic optical reconstruction microscopy (STORM).
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MOLECULAR PHARMACEUTICS
·
2018
·
IF 4.556
Kaili Wang,Chunjing Guo,Xue Dong,Yueming Yu,Bingjie Wang,Wanhui Liu,Daquan Chen
Many cancers, such as human breast cancer and lung cancer, easily metastasize to bones, leading to the formation of secondary tumors in advanced stages. On the basis of the CD44-targeted effect of oHA and the bone-targeted effect of ALN, we prepared a reduction-responsive, CD44 receptor-targeting and bone-targeting nanomicelle, called CUR-loaded ALN-oHA-S-S-CUR micelles. In this study, we aimed to evaluate the antitumor activity and bone-targeting ability of CUR-loaded ALN-oHA-S-S-CUR micelles. The in vivo experiment results showed that a larger number of micelles was gathered in the bone metastatic tumor tissue and reduced the bone destruction. The CUR-loaded ALN-oHA-S-S-CUR micelles markedly inhibited the tumor growth. So the CUR-loaded ALN-oHA-S-S-CUR micelles constitute a promising drug delivery system for bone tumor therapy.
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DRUG DELIVERY
·
2017
·
IF 6.402
Wei Chen,Lin Li,Xiaofen Zhang,Yuan Liang,Zhijun Pu,Lingfeng Wang,Jingxin Mo
Triple-negative breast cancer (TNBC) is a heterogeneous and clinically aggressive disease with no approved targeted therapy. Curcumin has shown therapeutic potential against TNBC, but it shows low bioavailability and low efficacy when administered as a free drug. Here we describe a novel vehicle for in vivo delivery of curcumin based on the phosphorylated calixarene POCA4C6. Curcumin-loaded POCA4C6 micelles (CPM) were prepared using the thin-film method and they showed a unilamellar structure with an average particle size of 3.86 nm. The micelles showed high curcumin encapsulation efficiency and loading was based on liquid chromatography-tandem mass spectrometry. Studies with cell cultures suggest that CPM can sustainably release curcumin in a pH-dependent manner. The micelles efficiently inhibited proliferation, invasion, migration and tumor spheroid formation by BT-549 human breast cancer cells. These effects involved increased apoptosis and reduced levels of nuclear β-catenin and androgen receptor. After injection into tumor xenografts, CPM persisted in the tumor tissue and efficiently inhibited tumor growth without causing obvious systemic toxicity. CPM also significantly reduced levels of CD44+/CD133+ breast cancer stem cells. Our results highlight the potential of CPM as an effective therapy against TNBC.
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INTERNATIONAL JOURNAL OF PHARMACEUTICS
·
2017
·
IF 3.649
Jiahao Lin,Qiang Cai,Yinian Tang,Yanjun Xu,Qian Wang,Tingting Li,Huihao Xu,Shuaiyu Wang,Kai Fan,Zhongjie Liu,Yipeng Jin,Degui Lin
Highly ordered mesoporous silica nanoparticles (MSNs) with pore diameter of 2.754 nm and particle size of 115 ± 15 nm were prepared with etching method. Homogeneous PEGylated lipid bilayer with 10–15 nm thickness was coated around the surface of MSNs using film hydration method. Systematic optimization and characterization of co-encapsulation process of paclitaxel (Tax) and curcumin (Cur) into PEGylated lipid bilayer coated mesoporous silica nanoparticles (PLMSNs) were performed carrying out single factor test, associated with Box-Behnken Design. The concentration of encapsulated drugs was measured by reversed phase high performance liquid chromatography (RP-HPLC) method. Optimal factor settings were as follows: 50 mg MSNs, ratio of MSNs to lipid (w/w) = 1:1.11, and ratio of lipid to CHO (w/w) = 3.93:1. The average experimental EE Tax , EE Cur and stability score value were (77.48 ± 2.73) %, (30.70 ± 3.56) % and 4 point respectively based on the conditions mentioned above. Morphology determination of Tax-Cur-PLMSNs revealed that the composite nanoparticles were spherical particals with uniform dispersion. In vitro release experiment indicated that PLMSNs improved dissolution of Tax compared to Tax powder suspension and exhibited sustained release property. Tax-Cur-PLMSNs manifested definite and persistently promoted cytotoxic effect against canine breast cancer cells. This prolonged and enhanced activity of Tax-Cur-PLMSNs might contribute to its sustained release effect.
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CARBOHYDRATE POLYMERS
·
2025
·
IF 12.5
Jin Feng,Zhen Wang,Xingyu Zhao,Lujing Xu,Cong Teng,Songbai Liu,Wuyang Huang,Ying Li
Oral targeted delivery systems for food bioactive compounds have attracted considerable attention for improving the efficiency of nutritional interventions. In this study, a hierarchical curcumin carrier with sequence-targeting capability was fabricated to mitigate colitis through a convenient and environmentally friendly approach. Initially, curcumin-loaded nanostructured lipid carriers (NLC) with hyaluronic acid (HA) moieties (HA-NLC) were prepared using ovalbumin-HA conjugates as emulsifiers. Subsequently, HA-NLC was immobilized within a calcium pectinate matrix using electrospray, leading to the formation of supramolecular microspheres (HA-NLC@MPs) approximately 140 μm in size. Results suggested that the pectin matrix preserved the integrity of the carrier and prevented curcumin leakage during transit through the upper gastrointestinal tract, while selectively degrading in response to colon bacteria. Moreover, the exposed HA moieties on the released HA-NLC facilitated the transcellular absorption of curcumin by inflamed colonic enterocytes through cluster of differentiation-44 receptor-mediated endocytosis. In vitro and in vivo studies demonstrated predominant curcumin accumulation in the colorectal tissues of colitis mice using HA-NLC@MPs as carrier. Curcumin delivered via HA-NLC@MPs demonstrated superior effects in alleviating colitis compared with that in the nanocarriers, through the modulation of macrophage polarization, TLR4/MyD88/NF-κB signaling cascade, and gut microbiota homeostasis.
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FOOD CHEMISTRY
·
2024
·
IF 8.5
Luhui Wang,Zihao Wei,Changhu Xue
To enhance the bioavailability of bioactives with varying efficacy in the gastrointestinal tract (GIT), a co-delivery system of solid-in-oil-in-water (S/O/W) emulsion was designed for the co-encapsulation of two bioactives in this paper. S/O/W emulsions were fabricated utilizing fucoxanthin (FUC)-loaded nanoparticles (NPs) as the solid phase, coconut oil containing curcumin (Cur) as the oil phase, and carboxymethyl starch (CMS)/propylene glycol alginate (PGA) complex as the aqueous phase. The high entrapment efficiency of Cur (82.3–91.3%) and FUC (96.0–96.1%) was found in the CMS/PGA complex-stabilized S/O/W emulsions. Encapsulation of Cur and FUC within S/O/W emulsions enhanced their UV and thermal stabilities. In addition, S/O/W emulsions prepared with CMS/PGA complexes displayed good stability. More importantly, the formed S/O/W emulsion possessed programmed sequential release characteristics, delivering Cur and FUC to the small intestine and colon, respectively. These results contributed to designing co-delivery systems for the programmed sequential release of two hydrophobic nutrients in the GIT.
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ADVANCED FUNCTIONAL MATERIALS
·
2024
·
IF 18.5
Jie Liao,Xiaoming Li,Huiqi Yang,Wei He,Bingbing Wang,Shuyu Liu,Yubo Fan
Postoperative adhesion (POA) has emerged as a prevalent clinical challenge in soft tissue repair, emphasizing the critical need for preventive measures. However, the complex POA development process makes POA prevention from a single aspect insufficient. Hence, a curcumin-loaded poly-L-lactic acid-poly (caprolactone) micro-nano conjugated fibrous membrane (PAPC MCFM (cur)) is engineered to synergistically prevent POA from multiple perspectives, in which poly (caprolactone) (PCL) nanofibers (118 ± 12 nm) with low orientation traverse the oriented poly-L-lactic acid (PLLA) microfibers (2.0 ± 0.3 µm). The PAPC MCFM not only significantly improves the mechanical properties of the anisotropic fibrous membrane (AIFM) that the modulus of elasticity and the tensile strength in the direction vertical to microfiber orientation increase by 4.5 and 13.0 times, respectively, but also can further enhance the “contact guidance effect” of AIFM, i.e., hindering fibroblast adhesion, proliferation, and differentiation to myofibroblast through inhibiting integrin β1 activation, vinculin expression and focal adhesion (FA) formation, and the nuclear localization activation of yes-associated protein (YAP). Except for these effects, PAPC MCFM loading with 2.5 mg mL −1 curcumin can further prevent POA by delivering anti-inflammatory, antioxidant, and antibacterial properties, and by suppressing fibrosis through decreased transforming growth factor-β1(TGF-β1) expression, showing effective POA prevention in rat abdominal cavity and rabbit dura mater models.
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MOLECULES
·
2016
·Vol. 21
·期 8
·1061
·
IF 2.465
Chongshan Dai,Daowen Li,Lijing Gong,Xilong Xiao,Shusheng Tang
Furazolidone (FZD), a synthetic nitrofuran derivative, has been widely used as an antibacterial and antiprotozoal agent. Recently, the potential toxicity of FZD has raised concerns, but its mechanism is still unclear. This study aimed to investigate the protective effect of curcumin on FZD-induced cytotoxicity and the underlying mechanism in human hepatocyte L02 cells. The results showed that curcumin pre-treatment significantly ameliorated FZD-induced oxidative stress, characterized by decreased reactive oxygen species (ROS) and malondialdehyde formation, and increased superoxide dismutase, catalase activities and glutathione contents. In addition, curcumin pre-treatment significantly ameliorated the loss of mitochondrial membrane potential, the activations of caspase-9 and -3, and apoptosis caused by FZD. Alkaline comet assay showed that curcumin markedly reduced FZD-induced DNA damage in a dose-dependent manner. Curcumin pre-treatment consistently and markedly down-regulated the mRNA expression levels of p53, Bax, caspase-9 and -3 and up-regulated the mRNA expression level of Bcl-2. Taken together, these results reveal that curcumin protects against FZD-induced DNA damage and apoptosis by inhibiting oxidative stress and mitochondrial pathway. Our study indicated that curcumin may be a promising combiner with FZD to reduce FZD-related toxicity in clinical applications.Keywords:curcumin;furazolidone;oxidative stress;DNA damage;mitochondrial pathway
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