Oncology Letters
·
2018
·Vol. 15
·期 5
·8079-8087
·
IF 1.664
Daren Liu,Xiaowen Li,Changlei Chen,Chao Li,Chuanbiao Zhou,Weidong Zhang,Jiangang Zhao,Jie Fan,Kai Cheng,Li Chen
Gastric cancer is the fourth most common malignancy globally. In order to decrease the dosage and side effects of conventional chemotherapy, and achieve improved benefits from molecular targeted therapy, novel drug delivery systems were developed in the present study. Oxaliplatin‑Au‑Fe3O4‑Herceptin® acts as a dual‑functional nanoparticles (NPs) conjugate and possesses the capability of human epithelial growth factor receptor 2 (HER2) targeting and oxaliplatin delivery. The 8‑20 nm Au‑Fe3O4 were synthesized by decomposing iron pentacarbonyl on the surfaces of Au NPs in the presence of oleic acid and oleylamine. Following being coated with polyethylene glycol, the NPs possessed a ζ‑potential of 13.8±1.6 mV and were demonstrated to exhibit no cytotoxicity when Fe concentration is <100 µg/ml via an MTS assay. Mass spectrometry analysis detected a peak at m/z 148,000, and Nuclear Magnetic Resonance indicated peaks at δ 3.51 (8.00H, s, 3‑H), 2.97‑3.02 (3.80H, t, 2‑H) and 2.72‑2.76 (3.72H, t, 1‑H) following successful loading with Herceptin and oxaliplatin probes. A drug release assay via dialysis cassettes demonstrated that 25% of the oxaliplatin was released at pH 8.0, however >58% was released at pH 6.0 following 4 h incubation, indicating its pH‑dependent release characteristic. The active targeting feature of oxaliplatin‑Au‑Fe3O4‑Herceptin was verified in a subcutaneous xenograft mouse model containing SGC‑7901 cells via detecting aggregated low intensity in T2‑weighted magnetic resonance imaging, which was further confirmed by immunohistochemistry. Therefore, oxaliplatin‑Au‑Fe3O4‑Herceptin is a promising multifunctional platform for simultaneous magnetic traceable and HER2 targeted chemotherapy for gastric cancer.
研究领域:
肿瘤学
·
纳米医学
·
药理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
CRYSTAL GROWTH & DESIGN
·
2020
·
IF 4.089
He-Mei Yin,Nan Wu,Bi-Jian Zhou,Ming-Huang Hong,Bin Zhu,Ming-Hui Qi,Guo-Bin Ren
Oxaliplatin (OXA) is a third-generation, platinum-based anticancer agent that is reported to induce cell toxicity in normal cells, which severely limits its applications. Its instability in aqua solution plays an important role in the cytotoxic effects. In this study, two novel drug–drug cocrystals of OXA were synthesized using baicalein (BAI) and naringenin (NAR) as cocrystal formers, as well as characterized by single crystal X-ray diffraction, powder X-ray diffraction, Fourier transform-infrared spectroscopy, and thermal analysis. Further evaluation of the dissolution profiles of the two cocrystals presented that they both have a reduced release rate and delayed hydrolysis compared to OXA. Theoretical analyses of the correlation between the structure and dissolution indicate that heterosynthons O–H···O and N–H···O hydrogen bonds are essential for reducing the dissolution rate of the two cocrystals. In addition, cell toxicity was studied using the CCK-8 assay, with the result that OXANAR may possess higher safety and OXABAI may have more significant effects on inhibiting cancer cells when compared to OXA.
研究领域:
药学
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肿瘤学
·
材料科学
✓ 已验证
产品关联
DOI
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2024
·
IF 7.7
Runrun Chi,Luqi Pan,Ziwei Yang,Xiao Yang,Hangbin Xia,Dan Lin,Jiahui Hao,Xiaoqin Si,Dongxue Yan,Huili Li,Changcan Shi,Yuqin Wang,Wenzhong Li
Hyaluronic acid (HA) nanogels have attracted widespread attention, aiming to improve cancer treatment paradigms and overcome the limitations of free-form drugs. However highly hydrophilic nature of HA nanogels limits their potential application where amphiphilic interactions are required for the delivery of hydrophobic drugs. In this study, we developed amphiphilic structure oxaliplatin (OXA) loaded oligo-hyaluronic acid (oHA)-PEG-Octane nanogel using stable disulfide bonds with ultrasonic re-emulsion method. 1,8-Mercaptooctane present in the organic phase underwent crosslinking with sulfhydryl groups conjugated on oHA and PEG in the inner aqueous phase through interfacial reactions, resulting in the formation of an amphiphilic structure of the nanogels. The nanogels demonstrated uniform size, stability, excellent biocompatibility, and achieved a high drug-loading capacity of 10.8 %. OXA NGs targeted tumor cells through CD44-mediated endocytosis, disassembled under the influence of high glutathione (GSH) levels within the tumor microenvironment (TME) and released OXA inside the reductive cytosol to trigger immunogenic cell death (ICD) of tumor cells. In vivo experiments showed OXA NGs could inhibit tumor growth. Furthermore, the amphiphilic hyaluronic acid nanohydrogel may have clinical potential due to its ability to accommodate various therapeutic agents; therefore, OXA NGs are a potential candidate for clinical translation.
研究领域:
药学
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生物医学工程
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肿瘤学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Journal of Materials Chemistry B
·
2014
·Vol. 2
·期 38
·6560-6570
·
IF 0
Haiqin Song,Haihua Xiao,Minhua Zheng,Ruogu Qi,Lesan Yan,Xiabin Jing
Anticancer drugs of gemcitabine and oxaliplatin combined in a clinic regimen (GEMOX regimen) were co-loaded to a biodegradable polymer platform for drug delivery.
研究领域:
药学
·
肿瘤学
✓ 已验证
DOI
PubMed
BIOLOGICAL & PHARMACEUTICAL BULLETIN
·
2023
·Vol. 46
·期 1
·26-34
·
IF 2
Chen Huang,Tao Zhou,Lihua Ma,Shipeng Zhao
Oxaliplatin (OXA) is a usual chemotherapeutic agent applied in the colorectal cancer (CRC) clinical treatment. Interferon-alpha inducible protein 6 (IFI6) has been proved to promote proliferation and suppress apoptosis in several tumor cells, while the impacts of IFI6 on OXA resistance in CRC still need exploration. HCT116 and SW620 cells were used as the parental to obtain OXA-resistant cells. The influence of IFI6 on OXA sensitivity, cell proliferation and apoptosis were evaluated by overexpression or knockdown IFI6 in cells. In this work, we found that the level of IFI6 was significantly enhanced in HCT116/OXA and SW620/OXA cells as compared to the parental cells. Overexpression of IFI6 decreased the sensitivity of HCT116 and SW620 cells to OXA. However, knockdown of IFI6 enhanced the sensitivity of HCT116/OXA and SW620/OXA cells to OXA. And upregulated IFI6 promoted the proliferation and repressed apoptosis in HCT116 cells, while suppressed IFI6 markedly reduced proliferation and increased apoptosis in HCT116/OXA cells. Additionally, IFI6 suppressed the phosphorylation level of p38, and silenced IFI6 enhanced it. The addition of the p38 kinase inhibitor, SB203580, alleviated the decreased cell proliferation and increased apoptosis in HCT116/OXA cells. Suppressed IFI6 enhanced the reactive oxygen species (ROS) level in HCT116/OXA cells, and blockade of ROS with N-acetyl-L-cysteine (NAC) decreased the enhancement level of ROS and the phosphorylation level of the p38, which was induced by IFI6 down-regulation. We, therefore, implied that suppressed IFI6 reverses OXA-resistance of CRC cells via promoting the ROS-induced p38 mitogen-activated protein kinase (MAPK) signaling pathway.
研究领域:
肿瘤学
·
分子生物学
·
细胞生物学
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药理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF BIOCHEMISTRY & CELL BIOLOGY
·
2024
·
IF 3.4
Yong Zhang,Zhiling Shen,Xiaodong Han,Yachao Wu,Tianchen Huang
Background Oxaliplatin is a first-line chemotherapy drug for colorectal cancer (CRC), but many patients eventually lose treatment efficacy due to acquired resistance. AC105118.1 is a long non-coding RNA with unknown biological function. This research attempts to probe into the molecular regulatory mechanism of AC105118.1 in CRC oxaliplatin resistance. Methods The expression level of AC105118.1 in CRC tissues and cells was measured based on The Cancer Genome Atlas (TCGA) data and quantitative reverse transcription polymerase chain reaction (qRT-PCR). We utilized dual-luciferase assay and RNA immunoprecipitation to analyze the interaction between AC105118.1, miR-378a-3p, and their downstream target KIF26B. CCK-8, colony formation assay, and flow cytometry were employed to assess the half inhibitory concentration (IC 50 ), cell proliferation, and apoptosis rate of HCT116/L-OHP cells treated with oxaliplatin. The glycolysis evaluation was completed by measuring the extracellular acidification rate (ECAR), glucose consumption, lactate production, and glycolysis-related proteins (HK2, GLUT1, and LDHA). TUNEL staining was used to detect the level of apoptosis. Results AC105118.1 was specifically upregulated in CRC tissues and cells. AC105118.1 indirectly facilitated the expression of miRNA target gene KIF26B by sequestering miR-378a-3p. In HCT116/L-OHP cells, transfection with si-AC105118.1 resulted in a decrease in glycolysis level, a lower maximum IC 50 required for oxaliplatin-treated cells, inhibited cell proliferation, and an increase in apoptosis rate. All of these effects were alleviated when simultaneously transfecting miR-378a-3p inhibitor or oe-KIF26B. Knockdown of AC105118.1 significantly inhibited oxaliplatin resistance to CRC in mice. Conclusion AC105118.1 facilitates glycolysis and increases CRC cells’ resistance to oxaliplatin by targeting the miR-378a-3p/KIF26B axis. The present work shed new insights into the function and mechanism of AC105118.1 in molecular function and suggested that the AC105118.1/miR-378a-3p/KIF26B axis is a promising target for intervening CRC oxaliplatin resistance.
研究领域:
分子生物学
·
肿瘤学
·
癌症研究
·
细胞生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ENVIRONMENTAL TOXICOLOGY
·
2023
·
IF 4.5
Yuan Tian,Wenwen Han,Long Fu,Kaiji Lv,Xinhua Zhou
Background Pancreatic cancer is one of the most aggressive tumors with a high-mortality rate. First-line drugs include 5-fluorouracil (5-FU), gemcitabine (GEM), and oxaliplatin (OXA). Resistance to 5-FU, GEM, and OXA is a major challenge. Immunoglobulin heavy chain F1 (IGHG1) participates in the regulation of cancer progression. It is still unclear how IGHG1 affects 5-FU, GEM, and OXA in pancreatic cancer. Methods The expression status of IGHG1 in pancreatic cancer was analyzed through bioinformatics tools. IGHG1 expression in pancreatic cancer tissues and cells was determined via RT–qPCR. Cell counting kit 8 assays, and flow cytometry analysis were utilized to detect the impact of IGHG1,5-FU, GEM, and OXA on cell proliferation and apoptosis. Western blotting was utilized to detect changes in the levels of the autophagy-associated proteins LC3, Beclin-1, p62, and ATG5. Immunofluorescence assays were employed to determine LC3 expression in cells. Xenograft experiments were conducted on nude mice to study tumor growth. Results IGHG1 was overexpressed in pancreatic cancer cells and tissues. IGHG1 expression was downregulated by 5-FU, GEM, or OXA treatment in cells. Treatment with 5-FU, GEM, or OXA repressed viability and promoted apoptosis and autophagy in pancreatic cancer cells. IGHG1 silencing exhibited the same results. Furthermore, IGHG1 depletion notably strengthened the effects of 5-FU, GEM, and OXA on pancreatic cancer cell viability, apoptosis, and autophagy. The combination of IGHG1 depletion with 5-FU, GEM, or OXA significantly reduced tumor growth in vivo. Conclusion Silencing of IGHG1 could enhance 5-FU, GEM, or OXA function in pancreatic cancer and reverse resistance by regulating apoptosis and autophagy.
研究领域:
肿瘤学
·
分子生物学
·
药理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ANALYTICAL CHEMISTRY
·
2023
·
IF 7.4
Ting Li,Wei Lu,Hui Tian,Yu Cao,Qianqian He,Xia Chen,Hailong Wang
The antitumor effect of Pt-based drugs is determined by their binding activity with deoxyribonucleic acid (DNA), and understanding the reaction process in a systematic manner is crucial. However, existing assays used for DNA–Pt research suffer from several issues, such as complicated sample preparation, preamplification, and expensive instruments, which dramatically limit their practical application. In this study, a novel method was presented to investigate the adducts of DNA and oxaliplatin using an α-hemolysin nanopore sensor. This approach allows for real-time monitoring of the DNA–oxaliplatin condensation process through the detection of nanopore events associated with DNA–oxaliplatin adducts. Specifically, type I and II signals exhibiting specific current characteristics were observed during the process. Typical signals with high frequency were obtained by recording the designed DNA sequence. Furthermore, the production of these signals was confirmed to be independent of homologous adducts. This finding suggests that the DNA–oxaliplatin adduct can serve as a potential sensor for detecting oxaliplatin lesions and multiple types of molecules.
研究领域:
生物物理学
·
纳米技术
·
癌症研究
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
International Journal of Biological Sciences
·
2019
·
IF 4.067
Peihai Cao,Yiqun Xia,Wei He,Tingting Zhang,Lin Hong,Peisen Zheng,Xin Shen,Guang Liang,Ri Cui,Peng Zou
Colon cancer is a malignant type of cancer with high prevalence and is one of the primary causes of cancer-related deaths. Oxaliplatin plays a significant role in the treatment of cancer, but the application of oxaliplatin is restricted due to its toxic side effects and drug resistance in clinical practice. Therefore, there is an urgent need for new strategies that can synergize with oxaliplatin for confronting colon cancer. Alantolactone (ALT), a natural sesquiterpene lactone, possesses antitumor properties in a number of cancer cell lines. In the present study, we investigated how ALT acts synergistically with oxaliplatin on human colorectal cancer HCT116 and RKO cells in vitro and in vivo . We observed that ALT strengthened the effect of oxaliplatin-induced growth restrain and apoptosis in HCT116 and RKO cells. It is through a mechanism concerning remarkable accumulation of intracellular reactive oxygen species (ROS) and activation of JNK and p38 MAPK signaling pathways. These changes ultimately induced apoptosis of HCT116 and RKO cells. Pretreatment of cells with the ROS reversal agent NAC significantly blocked the apoptosis induced by the combination treatment, and suppressed expression of JNK and p38 phosphorylation in HCT116 and RKO cells. In the xenograft model, the combination therapy displayed stronger antitumor activity compared with single agents. Immunohistochemistry of subsequent treatment tumors showed a significant decrease in proliferation as compared to either of the treatments alone. These results suggest that the combination treatment with ALT and oxaliplatin may become a potential therapeutic strategy for colon cancer.
研究领域:
肿瘤学
·
药理学
·
细胞生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
CHEMICAL ENGINEERING JOURNAL
·
2024
·
IF 13.3
Ping Sun,Li Huang,Zimu Li,Yao Yang,Shiman Lu,Nansha Gao,Hongzhong Chen,Xiaowei Zeng,Zhongjian Xie
Ferroptosis is a form of regulated cell death (RCD) induced by excessive lipid peroxidation, representing a promising mechanism for suppressing tumors. Herein, a type of nanoplatform (ODLP-PEGH8) was developed to harness the power of ferroptosis and immunogenic cell death (ICD) for the treatment of breast cancer. To enhance its effectiveness, this project incorporated a pH-responsive PEGH8 peptide onto the surface of the nanoplatform. This modification not only promoted charge reversal within the tumor microenvironment but also improved the cellular uptake efficiency of the nano-system, facilitating intracellular lysosomal escape. Subsequently, ODLP-PEGH8 rapidly degraded under conditions of low pH and exposure to light, resulting in the sequential release of the ferroptosis inducer lapatinib (LTB) and oxaliplatin (OXA). LTB induced ferroptosis and exhibited potent tumor cell-killing effects, while the ODLP-PEGH8, which possessed photothermal properties, worked with OXA to effectively induce ICD within the tumor. This dual approach triggered anti-tumor immune responses and had a substantial impact on tumor immunotherapy. All the results confirm that ODLP-PEGH8 mediates ferroptosis, enhancing the proliferation and infiltration of cytotoxic lymphocytes (CLTs) while demonstrating excellent biological safety in vivo. These findings suggest a promising therapeutic strategy for targeting ferroptosis in cancer treatment.
研究领域:
肿瘤学
·
生物材料学
·
免疫治疗
✓ 已验证
产品关联
DOI
高影响因子
POLYMERS FOR ADVANCED TECHNOLOGIES
·
2024
·Vol. 35
·期 4
·e6405
·
IF 3.1
Runrun Chi,Xiao Yang,Ziwei Yang,Hangbin Xia,Huili Li,Luqi Pan,Jiahui Hao,Dongxue Yan,Xiaoqin Si,Changcan Shi,Jie Sun,Wenzhong Li
Oxaliplatin (OXA) is widely utilized in clinical cancer treatment, however its effectiveness is hindered by drug resistance and severe side effects resulting from non-targeted delivery and lack of response to the tumor environment. In this research, thiol modified OXA and oligo hyaluronic acid (oHA) were used to developed a redox-responsive OXA-SS-oHA nanoparticle delivery system. The nanoparticles could release oxaliplatin prodrug OXA-SH through the cleavage of disulfide bonds in response of the abundant GSH in the tumor environment. OXA-SS-oHA nanoparticles were stable in aqueous solution for 7 days, and in vitro release experiments showed that the cumulative release of OXA in the absence of GSH was 21%, while in the presence of 10 mM concentration of GSH, the cumulative release was 47%. Additionally, OXA-SS-oHA demonstrated greater efficacy in inducing cell death in GSH-positive cells (MKN45) when compared to GSH-negative cells (L929). This study provides a novel strategy for the construction of GSH-stimulated responsive targeted drug delivery systems for cancer therapy.
研究领域:
药学
·
纳米技术
·
癌症研究
·
生物医学工程
✓ 已验证
产品关联
DOI
高影响因子
JOURNAL OF LIPOSOME RESEARCH
·
2025
·
IF 4.3
Zhicheng Su,Yanjiao Liu
This study aimed to design a novel liposome containing GA modified phosphatidylcholine lipid (GA-PC Lip) and determine its susceptibility to tumor over-expressed secretory phospholipase A2 (sPLA2) and its anti-cancer effect compared to conventional liposomes (Convention Lip). The liposomes were characterized for size, drug loading, encapsulation efficiency, and stability. A 6-CF release assay was conducted to assess the sensitivity of the liposomes to the tumor-overexpressed secretory phospholipase A2 (sPLA2). In vitro experiment, the sPLA2 levels in the Colo205 cell culture medium were detected by the Elisa kit and the anti-cancer effect of the oxaliplatin (L-OHP) loaded GA-PA Lip was analyzed by the CCK-8 assay. Results showed that both of L-OHP loaded formulations (GA-PC Lip and Convention Lip) had similar particle sizes of ∼100 nm and close entrapment efficiency values of 4.5–4.8%. The results of CF release assay indicated that the labeled GA-PC Lip had released more quickly than CF labeled Convention Lip in the presence of Bv sPLA2 and GA-PC Lip had a release of about 95% 6-CF at 2 h, whereas Convention Lip only released about 13% 6-CF. In addition, the average concentrations of sPLA2 in the cell-conditioned medium (CCM) of Colo205 cancer cells increased with incubation time and L-OHP loaded GA-PC Lip had much greater anti-proliferative activity than Convention Lip against Colo205 cells. These findings suggest that GA-PC Lip is an ideal complex for sPLA2-triggered release and has potential applications in enzyme-triggered smart anti-cancer drug release system to increase the anti-cancer effect.
研究领域:
药理学
·
肿瘤学
·
药物递送系统
·
生物化学
✓ 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）