INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2024
·
IF 7.7
Shu-Fang Li,Teng-Gen Hu,Yuan-Bao Jin,Hong Wu
In this study, the feasibility of shellac nanofibers as carrier system for colonic delivery of quercetin was evaluated. Firstly, the nanofibers without and with different amounts (2.5 %, 5.0 %, and 7.5 %) of quercetin were fabricated using pure shellac as a carrier by electrospinning. The morphology of nanofibers was bead-shape confirmed by SEM. FTIR, XRD, and DSC analysis showed that quercetin was encapsulated into shellac nanofibers, forming an amorphous complex. The molecular docking simulation indicated quercetin bound well to shellac through hydrogen bonding and van der Waals forces. These nanofibers had higher thermal stability than pure quercetin, and their surface wettability exhibited a pH-responsive behavior. The loading capacity of quercetin varied from 2.25 % to 6.84 % with the increased amount of quercetin, and it affected the stability of nanofibers in food simulants by measuring the release profiles of quercetin. The shellac nanofibers had high gastrointestinal stability, with a minimum quercetin release of 16.87 % in simulated digestive fluids, while the remaining quercetin was delivered to the colon and was released gradually. Moreover, the nanofibers exerted enhanced anticancer activity against HCT-116 cells by arresting cell cycle in G0/G1 phase and inducing cell apoptosis. Overall, shellac nanofibers are promising materials for colon-targeted delivery of active compounds.
研究领域:
药学
·
纳米技术
·
药物递送系统
·
癌症研究
·
材料科学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
MOLECULAR PHARMACEUTICS
·
2025
·
IF 4.5
Zhen Zhang,Hongbo Wang,Zhijun Zhang,Yaoyao Zhang,Huajing Sun,Xi Chen,Jiayu Gu,Yanling Gong
Small interfering RNA (siRNA)-based therapy, which silences disease-associated genes, has emerged as a potential therapeutic strategy for various disorders, including cancer. Lipid nanoparticles (LNPs) have become a leading platform for efficient siRNA delivery. SOX9, a family member of SRY-related high-mobility-group box (SOX) transcription factors, plays an important role in the pathogenesis and progression of colorectal cancer (CRC). Here, we developed cRGDfK peptide-modificed LNPs (R-LNPs) composed of DLin-MC3-DMA, DMG-PEG, DSPC, DSPE-PEG-cRGDfK, and cholesterol for the targeted delivery of SOX9 siRNA (siSOX9) in CRC treatment. The formulation, delivery, and antitumor effect on CRC in vitro and in vivo were explored. The optimized R-LNPs exhibited favorable physicochemical properties including a uniform particle size (159.6 ± 0.93 nm), low polydispersity index (PDI = 0.207 ± 0.016), near-neutral zeta potential (2.74 ± 0.35 mV), and high encapsulated efficiency (90.71 ± 1.63%). Additionally, R-LNPs demonstrated sustained and controlled in vitro release and good serum stability. The prepared R-LNPs were efficiently uptaken by HCT-116 via clathrin, lipid rafts, and caveolae dependent endocytosis and macropinocytosis. Subsequently, R-LNPs were colocalized with lysosomes before escaping into the cytoplasm, ensuring effective siRNA release. In vivo distribution studies confirmed tumor-specific accumulation for R-LNPs in HCT-116 xenograft models. Functionally, R-LNPs loading siSOX9 inhibited the proliferation, migration, and invasion of HCT-116 cells and Caco-2 cells (P < 0.05 or 0.01) and inhibited tumor growth and proliferation in tumor-bearing mice (P < 0.05 or 0.01). The antitumor effects were attributed to the silence of SOX9, which subsequently downregulated key oncogenic mediators, including β-catenin, cyclin D1, and c-Myc (P < 0.05 or 0.01). Furthermore, R-LNPs demonstrated favorable safety in in vivo application. In conclusion, our cRGDfK-modified LNPs loading siSOX9 represent a promising targeted therapeutic strategy for CRC, offering both efficacy and biocompatibility.
研究领域:
药剂学
·
肿瘤学
·
纳米技术
·
分子生物学
·
药物递送
·
生物技术
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ACS Applied Materials & Interfaces
·
2016
·
IF 7.145
Lisi Xie,Yan Tan,Zhiyong Wang,Hong Liu,Na Zhang,Chao Zou,Xin Liu,Gang Liu,Jian Lu,Hairong Zheng
RNA interference (RNAi) therapy is a promising treatment for various diseases. However, its application is still restricted by the lack of efficient and safe delivery systems. A novel siRNA delivery vehicle based on ε-caprolactone-modified polyethylenimine (PEI-CL) is presented here. The PEI-CL macromolecules with different grafting degrees were synthesized via a simple ring-opening reaction. This macromolecule strongly protects the siRNA from degradation in serum and promotes the cellular uptake and endosomal escape detected via chemical exchange saturation transfer magnetic resonance analysis and fluorescence imaging. The in vivo measurement was performed with HCT-116 colon tumor xenograft that stably expressed luciferase. The data showed that the PEI-CL/siRNA nanocomplexes elicited strong RNAi response. More interestingly, enhanced gene transfection efficiency was achieved by simultaneous cotransfection with siRNA and DNA plasmid via this novel nanosystem. Overall, our study suggests the PEI-CL macromolecule with great promise for siRNA delivery.
研究领域:
药学
·
生物技术
·
纳米技术
·
分子生物学
✓ 已验证
DOI
PubMed
高影响因子
Cancer Medicine
·
2021
·Vol. 10
·期 10
·3358-3372
·
IF 4.452
Dingsheng Liu,Chunsheng Chen,Mingming Cui,Hong Zhang
Recent studies have identified microRNAs (miRNAs) as a compelling novel class of biomarker in colorectal cancer (CRC) development and metastasis. Here, we demonstrated that the level of plasma exosomal miR-140-3p in CRC patients was lower than that in healthy controls. The decreased miR-140-3p level was also observed in CRC patients with liver metastasis. The expression of miR-140-3p in CRC tissues were significantly lower than that in matched normal tissues. Functionally, miR-140-3p overexpression suppressed proliferation, migration, invasion, and β-catenin nuclear translocation, as well as promoted apoptosis in LoVo cells, while inhibition of miR-140-3p reversed these cellular processes in HCT 116 cells. Notably, BCL9 and BCL2 were recognized as direct targets of miR-140-3p. BCL9 knockdown abrogated miR-140-3p inhibitor-induced effects on HCT 116 cells with decreased proliferation, migration, and invasion. BCL2 knockdown increased apoptosis of miR-140-3p inhibitor-transfected HCT 116 cells. In vivo experiments revealed that miR-140-3p overexpression inhibited tumor growth in LoVo xenograft model and diminished metastatic nodules in nude mice liver. Taken together, this work supports that miR-140-3p exerts as a tumor suppressor in CRC progression via targeting BCL9 and BCL2, and suggests miR-140-3p-BCL9/BCL2 axis may be applied in miRNA-based therapy and prognostication of CRC.
研究领域:
肿瘤学
·
分子生物学
·
癌症生物学
·
遗传学
✓ 已验证
DOI
PubMed
高影响因子
COLLOIDS AND SURFACES B-BIOINTERFACES
·
2016
·
IF 3.902
Shuangni Zhao,Le Van Minh,Na Li,Vasil M. Garamus,Ulrich A. Handge,Jianwen Liu,Rongguang Zhang,Regine Willumeit-Römer,Aihua Zou
The hydrophilic drug Doxorubicin hydrochloride (DOX) paired with oleic acid (OA) was successfully incorporated into nanostructured lipid carriers (NLCs) by a high-pressure homogenization (HPH) method. Drug nanovehicles with proper physico-chemical characteristics (less than 200 nm with narrow size distribution, spherical shape, layered internal organization, and negative electrical charge) were prepared and characterized by dynamic light scattering, zeta potential measurements, transmission electron microscopy, small-angle X-ray scattering and differential scanning calorimetry. The drug loading and entrapment efficiency of DOX-OA/NLCs were 4.09% and 97.80%, respectively. A pH-dependent DOX release from DOX-OA/NLCs, i.e., fast at pH 3.8 and 5.7 and sustained at pH 7.4, was obtained. A cytotoxicity assay showed that DOX-OA/NLCs had comparable cytotoxicity to pure DOX and were favorably taken up by HCT 116 cells. The intracellular distribution of DOX was also studied using a confocal laser scanning microscope. All of these results demonstrated that DOX-OA/NLCs could be a promising drug delivery system with tumor-specific DOX release for cancer treatment.
研究领域:
药学
·
纳米技术
·
癌症研究
·
药物递送系统
✓ 已验证
产品关联
DOI
PubMed
高影响因子
NANOTECHNOLOGY
·
2021
·Vol. 32
·期 45
·455101
·
IF 3.874
Xiaojing Yang,Di-Feng Chen,Lin-Song Li,Xue-Jie Zhao,Mei-Xia Zhao
In this study, a nanodrug carrier (mesoporous silica nanoparticle (MSN)-SS-cysteamine hydrochloride (CS)-hyaluronic acid (HA)) for targeted drug delivery was prepared using MSNs, in which HA was used as a targeting ligand and blocking agent to control drug release. Coumarin is a fluorescent molecule that targets mitochondria. Two conjugates (XDS-DJ and 5-FUA-4C-XDS) were synthesized by chemically coupling nitrogen mustard and 5-fluorouracil with coumarin, which was further loaded into MSN-SS-CS-HA nanocarriers. MTT analysis demonstrated that the nanocomposite MSN-SS-CS@5-FUA-4C-XDS/HA displayed stronger cytotoxicity toward HCT-116 cells than HeLa or QSG-7701 cells. Furthermore, MSN-SS-CS@5-FUA-4C-XDS/HA was able to target the mitochondria of HCT-116 cells, causing decreased mitochondrial membrane potential and excessive production of reactive oxygen species. These results indicate that MSN-SS-CS@5-FUA-4C-XDS/HA has the potential to be a nanodrug delivery system for the treatment of colon cancer.
研究领域:
纳米技术
·
药学
·
癌症研究
·
生物医学工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF MEDICINAL CHEMISTRY
·
2019
·
IF 6.054
Ran Zhang,Xue-Qing Song,Rui-Ping Liu,Zhong-Ying Ma,Jing-Yuan Xu
As FDA-approved chemotherapeutic agents, cisplatin, oxaliplatin, and 5-fluorouracil are widely used in clinic but limited by severe side-effects. To ameliorate their respective defects, a series of “dual-prodrug” by linking oxoplatin and 5-FU were designed and synthesized. The assembled compounds 10–17, named Fuplatin, exhibited much higher cytotoxicity against the tested cancer cells while lower cytotoxicity toward the human normal lung cells than free drugs or their combinations. Among them, 14 enhanced cellular accumulation with 62- and 825-fold amount of oxaliplatin and 8 at 9 h, respectively, significantly induced DNA damage and cell apoptosis, and inhibited migration and invasion in HCT-116 cells. Compound 14 arrested the cell cycle at S and G2 phases and up-regulated thymidylate synthase and p53, consistent with the results of the combination, suggesting 14 adopted a collaborative mode of 5-FU and oxaliplatin to kill cancer cells. In vivo, compound 14 showed high antitumor effect and no observable toxicity in NOD/SCID mice bearing HCT-116 tumors.
研究领域:
肿瘤学
·
药理学
·
化疗
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Acta Biomaterialia
·
2017
·
IF 6.319
Yi Chen,Haohuan Li,Yueyang Deng,Haifeng Sun,Xue Ke,Tianyuan Ci
The combination of chemotherapy and photothermal therapy is a promising strategy for cancer treatment. In the present study, indocyanine green (ICG), a widely used near-infrared (NIR) dye in photothermal therapy, and chemotherapeutic drug-doxorubicin (DOX) were loaded within the nanoparticles of novel designed arylboronic ester and cholesterol modified hyaluronic acid (PPE-Chol 1 -HA), denoted as PCH-DI. We take advantage of reactive oxygen species (ROS) production capability of ICG and ROS-sensitivity of arylboronic ester to realize controllable drug release. It was confirmed that PCH-DI exhibited remarkable photothermal effect and light-triggered faster release of DOX with NIR laser irradiation. DOX in PCH-DI/Laser group exhibited the most efficient nucleus binding toward HCT-116 colon cells in vitro . Furthermore, enhanced cytotoxicity and promoted tumor growth suppression effect of PCH-DI on HCT-116 tumor xenograft nude mice and AOM-induced murine orthotopic colorectal cancer model was achieved under NIR laser irradiation. Thus, the co-delivery system based on PCH appears to be a promising platform for the combined chemo-photothermal therapy in tumor treatment. Statement of Significance In case of chemo-photothermal combination therapy, the synchronism of treatments plays an important role in achieving expected antitumor efficiency. In this study, a light triggered ROS mediated drug delivery system was developed with the help of ROS-sensitive moieties of arylboronic ester and ROS producer of ICG. We innovatively make use of the ROS production capability of ICG under NIR laser irradiation to promote a faster release of DOX resulting from swelling of PCH-DI due to the presence of arylboronic ester. Intracellular ROS detection demonstrated that ROS level of PCH-I increased under irradiation. Moreover, the faster release behavior of DOX from PCH-DI with NIR laser irradiation was confirmed by the in vitro drug release and cellular uptake study. Meanwhile, local hyperthermia was verified by photothermal effect tests. Therefore, the synchronism of the combination therapy was achieved via light triggered faster release of DOX (chemo-therapy) and local hyperthermia (thermal-therapy) using PCH-DI under irradiation. It was reasonable to attribute the efficient anti-tumor efficiency of PCH-DI both in vitro and in vivo to the enhanced synergistic effect of chemo-photothermal combination therapy with realization of synchronism. To this end, this novel co-delivery system has provided a promising solution for achieving the synchronism of treatment to strengthen the efficiency of combination therapy.
研究领域:
癌症治疗
·
药物递送系统
·
纳米技术
·
光热治疗
·
化疗
✓ 已验证
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2024
·
IF 7.7
Shu-Fang Li,Teng-Gen Hu,Hong Wu
Quercetin possesses multiple biological activities. To achieve efficient colon-specific release of quercetin, new composite nanofibers were developed by coating pH-responsive shellac on hydrophilic gelatin through coaxial electrospinning. These composite nanofibers contained bead-like structures. The encapsulation efficiency (87.6–98.5 %) and loading capacity (1.4–4.1 %) varied with increasing the initial quercetin addition amount (2.5–7.5 %). FTIR, XRD, and TGA results showed that the quercetin was successfully encapsulated in composite nanofibers in an amorphous state, with interactions occurring among quercetin, gelatin, and shellac. Composite nanofibers had pH-responsive surface wettability due to the shellac coating. In vitro digestion experiments showed that these composite nanofibers were highly stable in the upper gastrointestinal tract, with quercetin release ranging from 4.75 % to 12.54 %. In vivo organ distribution and pharmacokinetic studies demonstrated that quercetin could be sustainably released in the colon after oral administration of composite nanofibers. Besides, the enhanced anticancer activity of composite nanofibers was confirmed against HCT-116 cells by analyzing their effect on cell viability, cell cycle, and apoptosis. Overall, these novel composite nanofibers could deliver efficiently quercetin to the colon and achieve its sustained release, thus potential to regulate colon health. This system is also helpful in delivering other bioactives to the colon and exerting their functional effects.
研究领域:
药学
·
纳米技术
·
生物医学工程
·
药物递送系统
·
癌症研究
✓ 已验证
产品关联
DOI
PubMed
高影响因子
RSC Advances
·
2018
·Vol. 8
·期 54
·31201-31212
·
IF 2.936
Xiaokang Long,Yao-Fu Zeng,Yunmei Liu,Ying Liu,Tangluo Li,Lanqing Liao,Yu Guo
Genistein amino acid derivatives 4a–4d were synthesized and evaluated for their cytotoxic activities against MCF-7, Hela, MGC-803 and HCT-116 cell lines by MTT assays in vitro. The results revealed that compounds 4a–4d showed better activity than the parent compound genistein. Particularly, compound 4b displayed the most significant anticancer activity against MGC-803 with an IC50 value of 12.08 μM. In addition, the mechanisms of interaction between genistein, compounds 4a–4d and BSA were investigated via multi-spectroscopic techniques such as ultraviolet (UV) spectroscopy, fluorescence, circular dichroism (CD), and molecular docking under physiological conditions. The results suggested that endogenous fluorescence of BSA could be quenched by genistein and compounds 4a–4d via forming BSA-compound complex, which meant a static quenching mechanism was involved. The negative values of enthalpy (ΔH) and entropy (ΔS) indicated that interactions between BSA and the ligands were spontaneous, and hydrogen bonding and van der Waals interactions were involved in the BSA-compound complexion formation. The UV, synchronous and 3D fluorescence results revealed that the micro-environment of tryptophan and conformation of BSA were changed after binding to ligands. CD analysis demonstrated the variation in the secondary structure and that the α-helix content of BSA decreased. Eventually, molecular docking was executed to forecast the binding forces and binding sites between BSA and compounds 4a–4d.
研究领域:
药理学
·
生物化学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Polymers
·
2023
·Vol. 15
·期 11
·2510
·
IF 5
Xuelian Chen,Lijia Liu,Chen Shen,Fangyan Liu,Enyu Xu,Yin Chen,Wang Jie
In recent years, natural polysaccharides have been widely used in the preparation of drug delivery systems. In this paper, novel polysaccharide-based nanoparticles were prepared by layer-by-layer assembly technology using silica as a template. The layers of nanoparticles were constructed based on the electrostatic interaction between a new pectin named NPGP and chitosan (CS). The targeting ability of nanoparticles was formed by grafting the RGD peptide, a tri-peptide motif containing arginine, glycine, and aspartic acid with high affinity to integrin receptors. The layer-by-layer assembly nanoparticles (RGD-(NPGP/CS)3NPGP) exhibited a high encapsulation efficiency (83.23 ± 6.12%), loading capacity (76.51 ± 1.24%), and pH-sensitive release property for doxorubicin. The RGD-(NPGP/CS)3NPGP nanoparticles showed better targeting to HCT-116 cells, the integrin αvβ3 high expression human colonic epithelial tumor cell line with higher uptake efficiency than MCF7 cells, the human breast carcinoma cell line with normal integrin expression. In vitro antitumor activity tests showed that the doxorubicin-loaded nanoparticles could effectively inhibit the proliferation of the HCT-116 cells. In conclusion, RGD-(NPGP/CS)3NPGP nanoparticles have potential as novel anticancer drug carriers because of their good targeting and drug-carrying activity.Keywords:layer-by-layer;nanoparticle;polysaccharide
研究领域:
药学
·
纳米技术
·
生物医学工程
·
癌症研究
✓ 已验证
产品关联
DOI
PubMed
高影响因子
EUROPEAN JOURNAL OF HISTOCHEMISTRY
·
2023
·
IF 2
Hui Yang,Yunlong Zhang,Desheng Zhang,Liping Qian,Tianxing Yang,Xiaocheng Wu
Crocin has been reported to have therapeutic effects on multiple cancers including colon cancer, but its specific mechanism is still ambiguous and needs to be further explored. Human colorectal adenocarcinoma cells (HCT- 116) and human normal colonic epithelial cells (CCD841) were first treated with increasing concentrations of crocin. Subsequently, with 150 and 200 μM of crocin, the cell vitality was examined by cell counting kit 8. Cell apoptosis and proliferation were tested by TUNEL staining and colony formation assay, respectively. The expression of Ki-67 was assessed by immunofluorescence. Enzyme-linked immunosorbent assay was used to evaluate the level of inflammation- and oxidative-related factors. The reactive oxygen species (ROS) production and mitochondrial membrane potential (MMP) were examined by flow cytometry. Janus kinase (JAK), signal transducer and activator of transcription 3 (STAT3), and extracellular regulated protein kinases (ERK) in HCT-116 cells were tested by Western blot. Different concentrations of crocin barely affected the CCD841 cell vitality, while crocin restrained the HCT-116 cells vitality, proliferation and the expression of Ki-67, while inducing apoptosis in a concentration-dependent manner. Moreover, the contents of inflammation- and oxidative- related factors in HCT-116 cells were largely blunted by crocin that enhanced ROS, restrained the MMP and suppressed p-JAK2/JAK2, p-STAT3/STAT3, and p-ERK/ERK expression. Crocin induced apoptosis and restored mitochondrial function in HCT-116 cells via repressing the JAK pathway. If the therapeutic effect works in patients, it could herald a new, effective treatment for colon cancer, improving the patients’ prognosis and quality of life.
研究领域:
癌症生物学
·
药理学
·
细胞生物学
·
分子生物学
✓ 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）