Frontiers in Medicine
·
2024
·
IF 3.1
Liu Yan,Ge Ri-Li,Shan Zhen-Zhen,Wang Yan-Jun,Yang Yan-Yan,Sun Xue,Luo Peng-Li
Podocytopathies encompass kidney diseases where direct or indirect podocyte injury leads to proteinuria or nephrotic syndrome. Although Semaphorin3A (Sema3A) is expressed in podocytes and tubular cells in adult mammalian kidneys and has a common effect on the progression of podocyte injury, its mechanism remains unclear. Previous studies have shown increased Sema3A expression in various glomerulopathies, indicating a gap in understanding its role. In this study, analysis of human data revealed a positive correlation between the levels of urinary Sema3A and Podocalyxin (PCX), suggesting a close relationship between Sema3A and podocyte loss. Furthermore, the impact of Adriamycin on podocytes was investigated. Adriamycin induced podocyte migration and apoptosis, along with an increase in Sema3A expression, all of which were ameliorated by the inhibition of Sema3A. Importantly, TRPC5 was found to increase the overexpression of Sema3A in podocytes. A TRPC5 inhibitor, AC1903, alleviated podocyte migration and apoptosis, inhibiting the formation of lamellar pseudopodia in the podocyte cytoskeleton by lowering the expression of Rac1. Furthermore, AC1903 relieved massive albuminuria and foot process effacement in the kidneys of Adriamycin-treated mice in vivo. In conclusion, our findings suggest that Sema3A may impact the cytoskeletal stability of podocytes through TRPC5 ion channels, mediated by Rac1, ultimately leading to foot process effacement. Notably, AC1903 demonstrates the potential to reverse Adriamycin-induced foot process fusion and urine protein. These results contribute to a deeper understanding of the mechanisms involved in podocytopathies and highlight the therapeutic potential of targeting the Sema3A-TRPC5 pathway.
研究领域:
肾脏病学
·
分子生物学
✓ 已验证
DOI
PubMed
高影响因子
EXPERIMENTAL CELL RESEARCH
·
2025
·
IF 3.5
Xiaofeng Ma,Wang chen,Zhihao Hu,Like Xie,Zhaobing Li,Huan Liu,Zili Li,Zhentao Jiang,Jiangwei Huang,Changrong Jiang,Ke Huang,Sujun Xiao
Background and aims The anthracycline chemotherapeutic agent doxorubicin (DOX) is widely used to treat cancer. However, DOX carries a high risk of adverse effects such as cardiovascular events. The aim of this study was to explore the role of Trim65 in DOX-induced cardiotoxicity (DIC) and its underlying mechanisms. Methods and Results Cellular studies were performed by exposing H9c2 cells (rat cardiomyocytes) to DOX. H9c2 cells were infected with lentivirus encoding negative control (LV-NC) or Trim65 (LV-Trim65). C57BL/6J mice were exposed to adeno-associated virus 9 (AAV9) containing cTnT promoter-encoded Trim65 sequence (AAV-Trim65) or AAV9 negative control sequence (AAV-NC) via tail vein injection. Furthermore, the following analysis were performed: cell viability, intracellular ROS production and lipid peroxidation. Echocardiography was used to measure the heart function of the mice. qPCR and western blotting were used to assess the expression of Trim65, p53, SLC7A11, and GPX4. According to our study, Trim65 expression was significantly downregulated in DIC. Overexpression of Trim65 exhibited considerable protection against to DIC, confirmed by both in vitro and in vivo experiments. In DOX-treated mice, mitochondria deformation was observed in the heart, as well as a high level of lipid peroxidation (signs of ferroptosis) and iron content, which were mitigated by overexpression of Trim65. Mechanistically, our study confirmed that DOX reduced the Trim65-mediated ubiquitination of p53, ultimately inhibiting the degration of p53. We also found that Trim65 mitigated DOX-induced ferroptosis via p53. Conclusion Collectively, our data demonstrated that Trim65 inhibits ferroptosis by degrading p53, thereby alleviating DIC. Therefore, Trim65 could be a promising target for the treatment of DIC.
研究领域:
分子生物学
·
心血管病学
·
肿瘤学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF NANOSCIENCE AND NANOTECHNOLOGY
·
2016
·Vol. 16
·期 6
·5740-5745
·
IF 1.338
Deng Jiangming,Mo Yunfei,Liu Jianghui,Guo Rui,Zhang Yi,Xue Wei,Zhang Yuanming
Inorganic nanoparticles have been widely used in biomedical field. In this paper, we try to study the use of three types of inorganic nanoparticles (i.e., SnS2, BiOCl and SnS2-incorporated BiOCl (SnS2/BiOCl)) as doxorubicin (DOX) carriers. Firstly, SnS2,
BiOCl and SnS2/BiOCl were synthesised, then were characterized by TEM, nanoparticles size and zeta potential. Next the drug release and cell viability test were carried out. The cell viability test indicated that the drug carriers can effectively kill HeLa cells while maintaining
low cytotoxicity against normal cells-fibroblasts. The results show the potential of SnS2/BiOCl nanoparticles for antitumor applications.
研究领域:
生物医学
·
药物递送
·
肿瘤学
✓ 已验证
DOI
PubMed
高影响因子
Chinese Journal of Natural Medicines
·
2020
·
IF 2.014
Yue YANG,Yan LIAO,Yan-Ping GUI,Li ZHAO,Lu-Bo GUO
Adriamycin resistance in HCC seriously hinders the treatment of patients, it is necessary to investigate the mechanisms. Autophagy is involved in adriamycin resistance and JNK2 is related to autophagy. However, whether JNK2 inducing drug resistance though autophagy is unknown. GL-V9, a new synthesized flavonoid derivative, has been proved of its anti-tumor effects. The aim of the study is to explore the role of JNK2-related autophagy on adriamycin-induced drug resistance and the effects of GL-V9 on reversing adriamycin resistance. We concluded that JNK2 played an important role in drug resistance induced by adriamycin. The high expression of JNK2 activated protective autophagy in Hep G2-DOXR cells under non-stress condition, which protected cells from drug attacking. Furthermore, we found that GL-V9 reversed adriamycin resistance by blocking the JNK2-related protective autophagy in HCC.
研究领域:
肿瘤学
·
分子生物学
·
药理学
✓ 已验证
DOI
PubMed
高影响因子
EUROPEAN JOURNAL OF PHARMACEUTICAL SCIENCES
·
2024
·
IF 4.3
Pei Huang,Gongfa Wu,Min Huang,Yating Deng,Xuming Chen,Guodong Ye,Xiyong Yu,He Wang,Huaying Wen,Yi Zhou
The resistance of tumor cells to apoptosis often leads to chemoresistance and treatment failure in clinic. In this study, we have developed a Cu 2+ -coordinated lignosulfonate (CLS) /doxorubicin (DOX) biological complex (referred to as LCD) with the aim of overcoming cellular resistance to apoptosis for combined lung cancer therapy. The copper complexes modified by CLS exhibit significant water solubility and excellent in vivo biocompatibility. The proportion of copper in the composite is simultaneously increased. Due to the coordination and π-π stacking effects, the self-assembled LCD exhibits nanometer-scale particle size, a narrow and homogeneous grain distribution, as well as excellent dispersion stability. Furthermore, LCD has the potential to disassemble in the presence of high levels of glutathione (GSH) and low pH, leading to effective drug release. Cu 2+ -mediated cuproptosis can lead to the down-regulation of FDX1 and DLAT protein expression by reducing mitochondrial membrane potential, resulting in non-apoptotic programmed cell death (PCD) regardless of cellular resistance to apoptosis. Moreover, the released DOX not only exhibits a preference for localizing in the cell nucleus to induce apoptosis for combined chemotherapy, but also generates a substantial amount of H 2 O 2 . This H 2 O 2 further produces ROS to induce apoptosis through Fenton reaction with Cu 2+ . LCD demonstrates significant superiority over monotherapy in inhibiting tumor growth while minimizing systemic toxicity through the combined action of cuproptosis and apoptosis. This study may provide a potential avenue for the advancement of self-delivery nanomedicine to overcome resistance to apoptosis in tumor therapy.
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
Current Drug Delivery
·
2024
·Vol. 21
·期 2
·295-307
·
IF 2.8
Yang Yaxin,Shi Wei,Zhang Ziyi,Gong Fawu,Feng Xuman,Guo Chenxi,Qi Yajuan,Liu Zhanjun
Introduction: Anti-inflammatory medications, in particular aspirin, have chemopreventive and anticancer adjuvant effects on specific types of cancers, according to ongoing anti-tumor research. Additionally, efforts have been made to transform Poly(salicylic acid) (PSA) into delivery-related
nanocarriers. to transport anticancer medications into nanocarriers. However, tumor cell targeting and tumor selectivity were lacking in the salicylic acid polymer-based nanocarriers, preventing them from performing to their full potential. Objective: The objective of this study is to
prepare targeting and reduction-responsive poly pre-drug nanocarriers (HA-ss-PSA NPs) and to investigate the feasibility of delivering adriamycin (DOX) as nanocarriers. Methods: The structures of the polymers were confirmed by nuclear magnetic resonance hydrogen spectroscopy (1H-NMR)
and infrared spectroscopy (IR); the encapsulation rate and drug loading of DOX-loaded nanoparticles were determined by HPLC; and the anti-tumor effects of the carriers were evaluated by MTT experiments and in vivoexperiments. Results: The prepared nanocarriers had uniform particle
size distribution. The drug release rate was up to 80% within 48 h in the tumor environment. DOX/HA-ss-PSA NPs showed significant cytostatic effects. In addition, HA-ss-PSA NPs showed significant targeting and inhibition of cell migration in cell uptake and scratch assays. In vivoexperiments
showed that the prepared carriers had high tumor inhibition rates, good targeting effects on the liver and tumor, and significantly reduced toxicity to other tissues. Conclusion: The prepared HA-ss-PSA NPs could effectively inhibit the growth of HepG2 cells and tumors in vivo,
indicating that PSA could be used as a backbone component of a safe and reliable drug delivery system, providing a new strategy for the treatment of liver cancer.
研究领域:
药学
·
肿瘤学
·
生物医学工程
✓ 已验证
DOI
PubMed
高影响因子
ACS Biomaterials Science & Engineering
·
2019
·
IF 4.511
Dian Li,Yue Song,Jinlin He,Mingzu Zhang,Peihong Ni
Click chemistry has increasing applications of the development of polymer materials and modification of drug carriers. The amino–yne click polymerization reacts quickly at room temperature without catalyst, and the enamine bond (-ena-) gained from the reaction is sensitive to acid and can be used to prepare stimulus-responsive polymeric prodrugs. Herein, we report an alkynyl-terminated polymer containing alternately distributed low molecular weight polyethylene glycol (PEG) and hexamethylenediamino (HMDA) linked by enamine bonds, abbreviated as A-P(PEG-alt-HMDA)-A, which was synthesized within 3 h at 35 °C without catalyst. The polymer was verified to have good water solubility, biocompatibility, and acid-sensitive fracturing. Then, a pH-responsive polymeric prodrug (DOX-ena-PPEG-ena-DOX) was further prepared through the amino–yne click reaction between the alkynyl groups of A-P(PEG-alt-HMDA)-A and the amino group of doxorubicin hydrochloride (DOX·HCl). The resulting prodrug can self-assemble into nanoparticles (NPs) in aqueous solution. The pH responsiveness of the prodrug NPs was demonstrated by a stability experiment of NPs and in vitro drug release behavior measurement. The accumulative release of doxorubicin (DOX) was tested with different pH media, which confirmed that the prodrug NPs could effectively dissociate and release drug under a weak acid microenvironment of lysosome/endosome. Subsequently, we investigated cell cytotoxicity and intracellular uptake of the prodrug. It turned out that the prodrug nanoparticles could be internalized into HeLa cells, release original DOX, and efficiently inhibit the proliferation of cancer cells. These results show that the pH-responsive DOX-ena-PPEG-ena-DOX has the potential for use in cancer therapy.
研究领域:
材料科学
·
药学
·
生物医学工程
✓ 已验证
DOI
高影响因子
JOURNAL OF COLLOID AND INTERFACE SCIENCE
·
2025
·
IF 9.7
Yanzhong Hao,Yaqiao Li,Wenfeng Zang,Yixin Sun,Xin Li,Lin Li,Zhonggui He,Bingjun Sun
Doxorubicin (DOX) is a vital anthracycline chemotherapeutic drug, yet presenting significant challenges due to its severe cardiotoxicity. While Doxil enhances the pharmacokinetics and reduces the cardiotoxicity of DOX solution (DOX sol), it shows limitations of low drug loading capacity and inadequate cellular uptake. To overcome these issues, this study developed a novel disulfide bond-linked DOX-maleimide prodrug (DSSM). DSSM could self-assemble into nanoparticles (NPs) with a high drug loading capacity (58.89 %, w/w). DSSM could rapidly bind to endogenous albumin through the maleimide group. Compared to DOX sol, DSSM had increased area under the curve (AUC) by approximately 60-fold, and similarly, quadrupled tumor accumulation after 4 h of administration, achieving efficient tumor targeting. With only 5 % DSPE-mPEG 2K , the cellular uptake of DSSM NPs was better than Doxil. Furthermore, the high reduction sensitivity of the disulfide bond enabled bio-activation of DSSM at the tumor site, while maintaining stability in normal cells. Compared with DOX sol and Doxil, DSSM NPs significantly improved safety and demonstrated better anti-tumor effect at tolerated doses. Our findings present a promising strategy for achieving effective tumor targeting and bio-activation, addressing key limitations of current DOX nanoformulations.
研究领域:
药学
·
肿瘤学
·
纳米医学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
DRUG DEVELOPMENT AND INDUSTRIAL PHARMACY
·
2015
·
IF 2.101
Zhuojun Gu,Meng Wang,Qiongyan Fang,Huaiyu Zheng,Feiyue Wu,Dai Lin,Ying Xu,Yi Jin
Context: Polyamidoamine (PAMAM) dendrimers have attracted lots of interest as drug carriers. And little study about whether pluronic-attached PAMAM dendrimers could be potential drug delivery systems has been carried on.Objective: Pluronic F127 (PF127) attached PAMAM dendrimers were designed as novel drug carriers.Methods: Two conjugation ratios of PF127-attached PAMAM dendrimers were synthesized. 1H nuclear magnetic resonance (1H-NMR), Fourier transform infrared spectrum (FTIR), element analysis and ninhydrin assay were used to characterize the conjugates. Size, zeta potential and critical micelle concentrations (CMC) were also detected. And DOX was incorporated into the hydrophobic interior of the conjugates. Studies on their drug loading and drug release were carried on. Furthermore, hemolysis and cytotoxicity assay were used to evaluate the toxicity of the conjugates.Results and discussion: PF127 was successfully conjugated to the fifth generation PAMAM dendrimer at two molar ratios of 19% and 57% (PF127 to surface amine per PAMAM dendrimer molecular). The conjugates showed an increased size and a reduced zeta potential. And higher CMC values were obtained than pure PF127. Compared with unconjugated PAMAM dendrimer, PF127 conjugation significantly reduced the hemolytic toxicity and cytotoxicity of PAMAM dendrimer in vitro. The encapsulation results showed that the ability to encapsulate DOX by the conjugate of 19% conjugation ratio was better than that of 57% conjugation ratio. And the maximum is ∼12.87 DOX molecules per conjugate molecule. Moreover, the complexes showed a sustained release behavior compared to pure DOX.Conclusion: Findings from the in vitro study show that the PF127-attached PAMAM dendrimers may be potential carriers for drug delivery.
研究领域:
药学
·
生物医学工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Polymer Chemistry
·
2024
·Vol. 15
·期 24
·2513-2527
·
IF 4.1
Shuai Yang,Jinhai Xie,Dongdong Wang,Shuangyu Tian,Yaodong Di,Lesan Yan
The distinct variations in the microenvironment between tumor cells and normal cells have facilitated the feasibility of highly specific and efficient drug delivery at tumor sites. This study is based on the elevated levels of glutathione (GSH) and NAD(P)H quinone oxidoreductase (NQO1 enzyme) in the tumor cells, leading to the development of a novel dual-responsive triblock polyurethane (PEG-PTU-SS-PEG) with heightened sensitivity to stimuli. This biodegradable amphiphilic polyurethane contains disulfide bonds responsive to GSH on the main chain and trimethyl locked benzoquinone structures responsive to NQO1 enzyme on the side chains. The polyurethane forms stable micelles through self-assembly and efficiently encapsulates the hydrophobic drug doxorubicin (DOX). Dynamic light scattering (DLS) and transmission electron microscopy (TEM) results indicate that both blank and drug-loaded micelles can be effectively disrupted upon addition of GSH or Na2S2O4 (simulating the NQO1 enzyme environment in vitro). Furthermore, the in vitro drug release behavior of drug-loaded micelles, cellular uptake, and cytotoxicity experiments demonstrate that in the presence of GSH and NQO1 enzyme, polyurethane nanomicelles can achieve specific and efficient drug release, enhance cytotoxicity against tumor cells, and maintain excellent biocompatibility. Therefore, this newly developed polyurethane nanodrug delivery system has tremendous potential in tumor therapy, offering specific drug release and efficient treatment.
研究领域:
药物递送
·
生物材料
·
肿瘤学
✓ 已验证
产品关联
DOI
高影响因子
JOURNAL OF BIOMATERIALS SCIENCE-POLYMER EDITION
·
2018
·
IF 1.911
Nahla Rahoui,Bo Jiang,Nadia Taloub,Mohammad Hegazy,Yu Dong Huang
The accuracy of spatiotemporal control cargo delivery and release are primordial to enhance the therapeutic efficiency and decrease the undesirable effects, in this context a novel prodrug were developed based on biocompatible polyvinyl alcohol (PVA) substrate. PVA was conjugated to doxorubicin (PVA-DOX) via an acid-labile hydrazone linkage. PVA was first functionalized with acidic groups, then reacted with hydrazine hydrate to form an amide bond. The amine group of PVA hydrazide was linked to carbonyl group (C = O) of DOX to form a pH sensitive hydrazone bond. The molecular structure of the PVA-DOX was confirmed by FTIR, XPS, and 1H-NMR analysis methods. The degree of grafting were evaluated by TGA and confirmed by XPS, which reveals the successful bond attachment of DOX to PVA. Our findings confirm pH dependent DOX release from PVA-DOX prodrug with faster release rate in acidic environment (pH 5.0, pH 6.0) and slower release rate in neutral pH environment (pH 7.4). Compared to the primary DOX, our synthesized PVA-DOX conjugates could exhibit a promising therapeutic effect, high biocompatibility and zero premature release. The results prove the successful synthesis of PVA-DOX conjugates with high efficiency.
研究领域:
药剂学
·
生物材料学
·
肿瘤学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
COLLOIDS AND SURFACES B-BIOINTERFACES
·
2018
·
IF 3.997
Min Yang,Houqiang Ding,Yixin Zhu,Yanxiu Ge,Lingbing Li
A strategy of preparing mixed micelles containing both DOX prodrug and PTX prodrug was developed, i.e., synthesizing a DOX conjugate and a PTX conjugate started with the same biocompatible amphiphilic copolymer, TPGS and DTDPA, a linker containing disulfide bond. The mixed micelles were prepared by co-assembling the two conjugates with a particle size about 98.5 nm. The mixed micelles could release anticancer drug DOX and PTX upon cellular reduction once they came into the cancerous cells. Moreover, the mixed micelles displayed synergistic effect in vitro and the combination therapy in micellar dosage-form led to reduced systematic toxicity and enhanced antitumor efficacy in vivo .
研究领域:
药剂学
·
肿瘤学
✓ 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）