INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2021
·
IF 6.953
Hui Xu,Ye Hu,Qiuhui Hu,Jianhui Liu,Anxiang Su,Minhao Xie,Gaoxing Ma,Fei Pei,Alfred Mugambi Mariga,Wenjian Yang
Flammulina velutipes has anti-inflammatory, immunomodulatory, antioxidant and many bioactive properties with high contents of carbohydrate, proteins and fibers. In this study, a novel proteoglycan with polysaccharide complexes and protein chain, named PGD1-1, was isolated from F. velutipes . The structural characteristics of PGD1-1 were then determined, and its anti-proliferation and pro-apoptotic activities against HepG-2 cells were demonstrated in vitro. Results proved that the average molecular weight of PGD1-1 was 32.71 kDa, and the carbohydrate and protein contents were 93.35 and 2.33%, respectively. The protein moiety was bonded to a polysaccharide chain via O-glycosidic linkage. The monosaccharides consisted of d -glucose, D-galactose and D-xylose in a molar ratio of 21.90:2.84:1.00. PGD1-1 significantly inhibited the proliferation of HepG-2 cells by affecting cell lipid peroxidation and nitric oxide production. In addition, PGD1-1 promoted the apoptosis of HepG-2 cells, especially the early apoptosis. These findings proved that PGD1-1 was a novel potent ingredient against the proliferation of HepG-2, which will provide a theoretical basis for the development and utilization of the functional ingredients of the F. velutipes .
研究领域:
分子生物学
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肿瘤学
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药理学
✓ 已验证
DOI
PubMed
高影响因子
Small
·
2014
·Vol. 10
·期 18
·3750-3760
·
IF 7.514
Jiangsheng Xu,Fang Zeng,Hao Wu,Caiping Hu,Changmin Yu,Shuizhu Wu
The therapeutic applications of exogenous nitric oxide are usually limited by its short half-life and its vulnerability to many biological substances, thus straightforward and precise spatiotemporal control of NO delivery may be critical to its therapeutic effects. Herein, the mitochondria-targeted and photoresponsive NO-releasing nanosystem is demonstrated as a new approach for cancer treatment. The nanosystem is fabricated by covalently incorporating a NO photo-donor and a mitochondria targeting ligand onto carbon-dots; accordingly, multi-functionalities (mitochondria-targeting, light-enhanced efficient NO-releasing, and cell imaging) are achieved. The in vitro NO release profiles for the nanosystem show that the duration of NO release from the present C-dot-based nanosystem containing immobilized SNO can be extended up to 8 hours or more. Upon cellular internalization, the nanosystem can target mitochondria and release NO. The action of the nanosystem on three cancer cell lines is evaluated; it is found that the targeted NO-releasing system can cause high cytotoxicity towards the cancer cells by specifically damaging their mitochondria. Additionally, light irradiation can amplify the cell apoptosis by enhancing NO release. These observations demonstrate that incorporating mitochondria-targeting ligand onto a NO-releasing system can enhance its pro-apoptosis action, thereby providing new insights for exploiting NO in cancer therapy.
研究领域:
药理学
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癌症研究
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纳米医学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Science Advances
·
2020
·Vol. 6
·期 33
·
IF 13.117
Guangyu Rong,Changping Wang,Lijie Chen,Yang Yan,Yiyun Cheng
Cytosolic delivery of peptides remains a challenging task owing to their susceptibility to enzymatic degradation and the existence of multiple intracellular barriers. Here, we report a new strategy to address these issues by decoration of a fluorous tag on the terminal of cargo peptides. The fluorous-tagged peptides were assembled into nanostructures, efficiently internalized by cells via several endocytic pathways and released into the cytosol after endosomal escape. They were relatively stable against enzymatic degradation and showed much higher efficiency than nonfluorinated analogs and cell penetrant peptide–conjugated ones. The proposed strategy also efficiently delivered a proapoptotic peptide into specific sites in the cells and restored the function of cargo peptide after cytosolic delivery. The fluorous-tagged proapoptotic peptide efficiently inhibited tumor growth in vivo. This study provides an efficient fluorination strategy to promote the cytosolic delivery of peptides.
研究领域:
药学
·
生物化学
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细胞生物学
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生物技术
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药物化学
✓ 已验证
DOI
高影响因子
Expert Opinion on Drug Delivery
·
2014
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IF 4.116
Jinming Zhang,Yingbo Li,Wei Gao,Michael A Repka,Yitao Wang,Meiwan Chen
Background: Andrographolide (ADG) isolated from Andrographis paniculata exhibits anti-inflammatory and anticancer activities, but high hydrophobicity and poor bioavailability greatly restricts its clinical application.Objectives: In this study, ADG was encapsulated in a micelle formulation based on poly (D,L-lactide-co-glycolide)-b-poly (ethylene glycol)-b-poly (D,L-lactide-co-glycolide) (PLGA-PEG-PLGA) amphiphilic triblock copolymers, in order to enhance the anticancer efficacy and bioavailability in vivo.Methods: The physicochemical properties of the ADG-loaded PLGA-PEG-PLGA micelles were investigated for encapsulation efficiency, particle size, zeta potential and critical micelle concentration. These micelles were further evaluated for in vitro cytotoxicity, including proliferation inhibition, cell cycle arrest and pro-apoptosis effects against human breast cancer MAD-MB-231 cells, cellular uptake and pharmacokinetics study in rat.Results: ADG-loaded PLGA-PEG-PLGA micelles had a high encapsulation and loading efficiency of about 92 and 8.4% (w/w), respectively, and a stable particle size of 124.3 ± 6.4 nm. In vitro cytotoxicity testing demonstrated that ADG-loaded PLGA-PEG-PLGA micelles exhibited higher proliferation inhibition, cell cycle arrest at the G2/M phase and pro-apoptosis effects in MAD-MB-231 cells, which would be contributed to higher efficiency of cellular uptake and intracellular transport. Further, the plasma AUC(0 – ∞) and mean resident time of ADG-loaded PLGA-PEG-PLGA micelles were increased by 2.7- and 2.5-fold, respectively, when compared to the raw suspension.Conclusion: All of these investigations suggest that PLGA-PEG-PLGA micelles may be a potential drug delivery strategy for improving ADG bioavailability and efficacy in cancer therapy.
研究领域:
药剂学
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肿瘤学
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纳米医学
✓ 已验证
DOI
PubMed
高影响因子
Drug Design Development and Therapy
·
2023
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IF 4.8
Zhen Yu,Shixin Chan,Xu Wang,Rui Sun,Ming Wang,Zhenglin Wang,Xiaomin Zuo,Jiajie Chen,Huabing Zhang,Wei Chen
Purpose To evaluate the effect of 5-fluorouracil (5-FU) combined with rutaecarpine (RUT) on the antiproliferative, anti-migratory, and apoptosis-promoting ability of colorectal cancer (CRC) cells and explore the underlying mechanism.Methods The antiproliferative effects of RUT and 5-FU on CRC cells were evaluated using MTT and colony formation assays. Anti-migration was assessed by cell scratch and transwell tests. The synergistic effect of RUT and 5-FU was assessed by isobologram and combination index analysis using CompuSyn software. The effects of RUT and 5-FU on cell apoptosis were detected by flow cytometry. Differences in protein expression levels with or without RUT and/or 5-FU treatment were assessed by Western blot. Moreover, a mouse xenograft model of CRC was established to investigate the antitumor effect of RUT and 5-FU in vivo, and Ki67 and cleaved caspase-3 expression was detected by immunofluorescence.Results In this study, we found that 5-FU combined with RUT can inhibit the proliferative, migratory, and antiapoptotic abilities of CRC cells to a significantly greater extent than either RUT or 5-FU alone both in vivo and in vitro. Western blot analysis showed that the level of signal transducer and activator of transcription 3 (STAT3) phosphorylation in CRC cells was significantly reduced after combination therapy compared with that seen with the respective monotherapies. In addition, combination therapy influenced the STAT3 signaling pathway, namely, it inhibited the expression of c-Myc, CDK4, and Bcl-2 while enhancing that of the proapoptotic protein cleaved caspase-3. Immunofluorescence staining further showed that the expression of Ki67 and cleaved caspase-3 was significantly downregulated and upregulated, respectively, in tumor tissues of mice treated with combination therapy compared with that observed with 5-FU treatment alone.Conclusion Combined therapy with 5-FU and RUT exerted a superior curative effect in CRC than treatment with either single drug alone and has potential as a novel therapeutic modality for the treatment of CRC.
研究领域:
肿瘤学
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药理学
·
分子生物学
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细胞生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Nanoscience and Nanotechnology Letters
·
2018
·Vol. 10
·期 10
·1387-1393
·
IF 2.917
Liu Xiaoning,Xu Yuling,Kang Jingjing,Wang Hui,Huang Tao
Mesoporous Silica Nanoparticles (MSNs) loaded with lycorine were previously reported to induce apoptosis of prostate cancer cells with remarkably enhanced efficiency and reduced side effects. In the current study, MSNs-based co-delivery of lycorine and/or the tumor suppressor gene p53
was developed for drug delivery to chronic myelocytic leukemia (CML) cell line K562. We have demonstrated that the simultaneous delivery of lycorine and p53 via MSNs achieved synergistic anti-proliferative and pro-apoptotic effects on K562 cells when compared to MSNs loaded with lycorine only.
The cell viability assay on K562 cells showed that the half-maximal inhibitory concentration (IC50) after 48 h of treatment with MSNs@Lycorine@pcDNA3.1-p53 was only 20% of that for MSNs@Lycorine. Furthermore, the Annexin V-FITC/PI assay for K562 cell apoptosis demonstrated a markedly
higher apoptotic rate in the group treated with MSNs@Lycorine@pcDNA3.1-p53 when compared to that of the MSNs@Lycorine group; this result was consistent with the accumulation of the p53 protein. These findings indicate that MSNs could be an ideal nanovector for simultaneous delivery of drugs
and genes for improved cancer therapy and that an MSN-based lycorine/wt-p53 co-delivery system with efficient endocytosis, sustained drug-releasing property, excellent biocompatibility, and enhanced synergistic proapoptotic effects might be a new promising strategy for the treatment of CML.
研究领域:
药学
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肿瘤学
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纳米医学
✓ 已验证
DOI
高影响因子
JOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH
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2019
·Vol. 38
·期 1
·1-13
·
IF 5.646
Yang Lehe,Lin Shichong,Kang Yanting,Xiang Youqun,Xu Lingyuan,Li Jifa,Dai Xuanxuan,Liang Guang,Huang Xiaoying,Zhao Chengguang
Background Rhein is a lipophilic anthraquinone extensively found in medicinal herbs. Emerging evidence suggests that rhein has significant antitumor effects, supporting its potential use as an antitumor agent. The IL6/STAT3 signaling pathway has been suggested as an attractive target for the discovery of novel cancer therapeutics.Methods The human pancreatic cancer cell lines AsPC-1, Patu8988T, BxPC-3 and PANC-1, and immunodeficient mice were chosen as models to study the effects of rhein. The potent antiproliferative and proapoptotic effects of rhein were examined by cell viability, cellular morphology, apoptosis and colony formation assays. The STAT3 luciferase report assay, immunostaining analysis and Western blot analysis revealed the inhibition of the IL6/STAT3 signaling axis.Results Apoptosis was induced by adjunctive use of rhein with epidermal growth factor receptor (EGFR) inhibitors in pancreatic cancer cells as verified by cell apoptosis analysis and changes in the expression level of apoptotic/anti-apoptotic proteins BCL-2, BAX, Caspase 3 and Cl-PARP. Suppression of the phosphorylation of STAT3 and EGFR were also observed as a result of the treatment with a combination of rhein and EGFR inhibitors. Most interestingly, it was found that rhein considerably sensitized cells to erlotinib, thus suppressing tumor growth in PANC-1 and BxPC-3 xenograft models. The in vivo anti-tumor effect was associated with increased apoptosis and combined inhibition of the STAT3 and EGFR pathways in tumor remnants.Conclusion sRhein sensitizes human pancreatic cancer cells to EGFR inhibitors through inhibition of STAT3. Taken together, the results indicate that rhein offers a novel blueprint for pancreatic cancer therapy, particularly when combined with EGFR inhibitors.
研究领域:
肿瘤学
·
药理学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Frontiers in Oncology
·
2021
·
IF 6.244
Guo Wei,Ma Xingyuan,Fu Yunhui,Liu Chang,Liu Qiuli,Hu Fabiao,Miao Hui,Zhang Tong,Liu Yuping,Han Myong Hun,You Fang,Yang Yi,Zheng Wenyun
Survivin as a member of the inhibitor of apoptosis proteins (IAPs) family is undetectable in normal cells, but highly expressed in cancer cells and cancer stem cells (CSCs) which makes it an attractive target in cancer therapy. Survivin dominant negative mutants have been reported as competitive inhibitors of endogenous survivin protein in cancer cells. However, there is a lack of systematic comparative studies on which mutants have stronger effect on promoting apoptosis in cancer cells, which will hinder the development of novel anti-cancer drugs. Here, based on the previous study of survivin and its analysis of the relationship between structure and function, we designed and constructed a series of different amino acid mutants from survivin (TmSm34, TmSm48, TmSm84, TmSm34/48, TmSm34/84, and TmSm34/48/84) fused cell-permeable peptide TATm at the N-terminus, and a dominant negative mutant TmSm34/84 with stronger pro-apoptotic activity was selected and evaluated systematically in vitro. The double-site mutant of survivin (TmSm34/84) showed more robust pro-apoptotic activity against A549 cells than others, and could reverse the resistance of A549 CSCs to adriamycin (ADM) (reversal index up to 7.01) by decreasing the expression levels of survivin, P-gp, and Bcl-2 while increasing cleaved caspase-3 in CSCs. This study indicated the selected survivin dominant negative mutant TmSm34/84 is promising to be an excellent candidate for recombinant anti-cancer protein by promoting apoptosis of cancer cells and their stem cells and sensitizing chemotherapeutic drugs.
研究领域:
肿瘤学
·
分子生物学
·
癌症治疗
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Nano Research
·
2023
·
IF 9.9
Qu Haijing,Chen Han,Cheng Wei,Pan Yuqing,Duan Zhiran,Wang Yanjun,Liang Xing-Jie,Xue Xiangdong
Although anti-cancer nanotherapeutics have made breakthroughs, many remain clinically unsatisfactory due to limited delivery efficiency and complicated biological barriers. Here, we prepared charge-reversible crosslinked nanoparticles (PDC NPs) by supramolecular self-assembly of pro-apoptotic peptides and photosensitizers, followed by crosslinking the self-assemblies with polyethylene glycol to impart tumor microenvironment responsiveness and charge-reversibility. The resultant PDC NPs have a high drug loading of 68.3%, substantially exceeding that of 10%–15% in conventional drug delivery systems. PDC NPs can overcome the delivery hurdles to significantly improve the tumor accumulation and endocytosis of payloads by surface charge reversal and responsive crosslinking strategy. Pro-apoptotic peptides target the mitochondrial membranes and block the respiratory effect to reduce local oxygen consumption, which extensively augments oxygen-dependent photodynamic therapy (PDT). The photosensitizers around mitochondria increased along with the peptides, allowing PDT to work with pro-apoptotic peptides synergistically to induce tumor cell death by mitochondria-dependent apoptotic pathways. Our strategy would provide a valuable reference for improving the delivery efficiency of hydrophilic peptides and developing mitochondrial-targeting cancer therapies.
研究领域:
纳米技术
·
癌症治疗
·
药物递送系统
·
分子生物学
✓ 已验证
产品关联
DOI
高影响因子
LANGMUIR
·
2019
·
IF 3.683
Jing Zhang,Liqun Chen,Biao Shen,Lingdong Chen,Jiaying Mo,Jie Feng
A dual-sensitive drug delivery system (DDS) based on graphene oxide (GO) which is simultaneously loaded with proapoptotic peptides and anticancer drugs was rationally designed and fabricated for cancer synergetic therapy. Specifically, a kind of cell apoptosis peptide (KLAKLAK)2 (KLA) was anchored on the surface of GO via a disulfide bond to obtain GO-SS-KLA. Then, the aromatic anticancer drug doxorubicin (DOX) was loaded on GO through π–π conjugation and hydrogen bonding interactions. Finally, bovine serum albumin (BSA) was used to coat the GO carrier to obtain a biological medium-stable GO-based DDS, DOX@GO-SS-KLA/BSA. The results show that KLA and DOX can be released responding to the reductive and pH stimulus inside the cells, respectively, and achieve a synergetic therapy for cancer. Moreover, the results of stability studies show that DOX@GO-SS-KLA/BSA could be stably dispersed in water for more than 8 days and in 10% fetal bovine serum for at least 6 days. The constructed DOX@GO-SS-KLA/BSA exhibits great potential as a drug carrier for co-delivery of various therapeutic agents.
研究领域:
纳米医学
·
癌症研究
·
药物递送
·
生物材料科学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
COLLOIDS AND SURFACES B-BIOINTERFACES
·
2016
·
IF 3.902
Yaqing Jin,Nengpan Zhang,Chunlin Li,Kefeng Pu,Chen Ding,Yimin Zhu
A dual-functional delivery system, based on mesoporous silica nanoparticles (MSNs) with the integration of Magnetic Resonance (MR) imaging and therapeutic peptide delivery, is reported in this paper. A lipid bilayer is attached onto the surface of the nanoparticles, following the doping of Gadolinium (Gd), a paramagnetic lanthanide ion. The liposome-coated GdMSNs exhibit improved colloidal stability, better biocompatibility and more efficient cellular uptake. The Gd renders the nano carrier a potential T1 contrast agent, confirmed by the MR imaging. A pro-apoptotic peptide, KLA (HGGKLAKLAKKLAKLAK), is encapsulated into the GdMSNs-LP and enters into the cells successfully to induce mitochondrial swelling and apoptosis, while it is nontoxic outside the cells. The synthesis procedure is convenient and free of toxic organic reagents. The nanosystem we construct may contribute to a promising theranostic platform for therapeutic peptide delivery in cancer treatment.
研究领域:
纳米技术
·
生物医学工程
·
癌症研究
·
材料科学
·
药学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
CHEMICAL ENGINEERING JOURNAL
·
2022
·
IF 16.744
Weipan Peng,Shenghui Li,Yating zhang,Qiuting Zhang,Wenna Li,Houyu Han,Dianming Zhou,Sheng Wang,Jin Chang,Xiaoqun Gong
Tumors progression is usually characterized by proliferation, migration, and angiogenesis , and it leads to uncontrolled tissue growth and blocks the mechanism of apoptosis. Therefore, targeted angiogenesis and anti-apoptosis is considered promising therapeutic strategy for cancer prevention and treatment. Herein, we report a versatile and intelligent MnO 2 -PEI-DNAzymes (MnPDs) nanodevice for self-sufficient anti-tumor angiogenesis and pro-apoptosis synergistic gene silencing, coupling multi-target bimodal in situ imaging. Intracellularly, the multifunctional charge-reversal MnPDs undergo reduction and lysis by the overexpressed GSH, actualizing enhanced MR imaging and sufficient DNAzyme cofactors in tumor tissue, and enabling miRNA-155 and telomerase biomarkers dual-fluorescence imaging. Under the precise multimodal imaging, the dual DNAzymes enable self-sufficient Early growth response-1 (EGR1) and Survivin (SUR) mRNAs synergistic silencing, effectively inhibiting tumor angiogenesis and anti-apoptotic. Considering that accurate and efficient therapy has become a trend in cancer therapy, our proposed self-sustaining multifunctional nanodevice is promising for broad clinical applications.
研究领域:
癌症生物学
·
纳米技术
·
基因治疗
·
分子成像
·
生物医学工程
✓ 已验证
产品关联
DOI
高影响因子
危险品化学品经营许可证（带存储）