JOURNAL OF DRUG DELIVERY SCIENCE AND TECHNOLOGY
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2024
·
IF 4.5
Yu Wang,Lisi Yan,Xu Yan,Jianqiang Ding,Bo Cheng,Jing Yang,Binbin Li,Xinyu Wang
The micro-nano structure of drug delivery systems, which realize the release of the drug in stages, represent a promising therapeutic approach for tumor chemotherapy. In this study, we developed a drug delivery system in which nano-PLGA was coated on the surface of attapulgite microspheres (ATT-MS) loaded with doxorubicin hydrochloride (DOX). Nano-PLGA surrounding ATT-MS formed a satellite structure, which improved the drug release rate by blocking the drug release channels with the nano-PLGA. The drug delivery system achieves a high DOX encapsulation efficiency (98 %) and enables passive, tumor-selective drug release. The zeta potential and drug release curve showed that DOX in this drug delivery system is more readily released in the tumor microenvironment. The fluorescence imaging and Western blot analysis showed that the drug delivery system has the potential to improve tumor resistance. Moreover, the in vivo experiment showed that the system not only maintained the anticancer activity but also reduced the organ damage. In conclusion, this micro-nano structure of the drug delivery system may provide a novel approach to effectively deliver DOX to the tumor and reduce systemic toxicity.
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高影响因子
COLLOIDS AND SURFACES B-BIOINTERFACES
·
2025
·
IF 5.6
Wenjing Li,Juan Shao,Chuxin Zhang,Guodong Cao,Yitao Yan,Qiongyi Han,Huimei Yu,Yingying Wei,Wenbo Zhang,Jie Zheng,Zhongyuan Guo
Colorectal cancer has emerged as a leading cause of global cancer-related morbidity and mortality, necessitating innovative therapeutic strategies. We developed a desilication-recrystallization method to synthesize Silicalite-1-X (X = 2, 8, 16, 32), a hierarchical porous silica molecular sieve with cost-effectiveness, facile synthesis, and tunable porosity. Its programmable mesoporous structure is achieved by precisely controlling the desilication-recrystallization kinetics. Tunable mesopores with precise diameters of 4–6 nm and 20–30 nm were fabricated by controlling cavity expansion through temporal modulation (2–32 h) of a time-dependent synthesis process. Detailed analysis of drug loading and release profiles revealed that although pore structure modification did not significantly alter drug loading efficiency (DLE), it induced a slight but consistent improvement in drug release rate as pore size increased. Systematic biocompatibility evaluation was conducted through an in vitro human colonic epithelial tissue model complemented by the KM mice in vivo studies. Histopathological analysis confirmed Silicalite-1-X caused minimal cytotoxicity and oxidative stress in healthy colon tissue, preserved mucus secretion, and showed no systemic toxicity. Furthermore, Doxorubicin (DOX) loaded Silicalite-1-X platform (Silicalite-1-DOX-X) exhibited dose-dependent cytotoxic efficacy against colorectal carcinoma in vitro models, confirming its anti-tumor therapeutic potential. Our findings provide a framework for engineering molecular sieves with tunable porosity and a platform for expanding their multifunctional applications in advanced materials.
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ARCHIVES OF TOXICOLOGY
·
2024
·
IF 4.8
Wang Yanwei,Qiu Jingru,Yan Hua,Zhang Nan,Gao Shixuan,Xu Ning,Wang Cuiyan,Lou Haiyan
Doxorubicin (DOX) is one of the most frequently used chemotherapeutic drugs belonging to the class of anthracyclines. However, the cardiotoxic effects of anthracyclines limit their clinical use. Recent studies have suggested that ferroptosis is the main underlying pathogenetic mechanism of DOX-induced cardiomyopathy (DIC). BTB-and-CNC homology 1 (Bach1) acts as a key role in the regulation of ferroptosis. However, the mechanistic role of Bach1 in DIC remains unclear. Therefore, this study aimed to investigate the underlying mechanistic role of Bach1 in DOX-induced cardiotoxicity using the DIC mice in vivo (DOX at cumulative dose of 20 mg/kg) and the DOX-treated H9c2 cardiomyocytes in vitro (1 μM). Our results show a marked upregulation in the expression of Bach1 in the cardiac tissues of the DOX-treated mice and the DOX-treated cardiomyocytes. However, Bach1 −/− mice exhibited reduced lipid peroxidation and less severe cardiomyopathy after DOX treatment. Bach1 knockdown protected against DOX-induced ferroptosis in both in vivo and in vitro models. Ferrostatin-1 (Fer-1), a potent inhibitor of ferroptosis, significantly alleviated DOX-induced cardiac damage. However, the cardioprotective effects of Bach1 knockdown were reversed by pre-treatment with Zinc Protoporphyrin (ZnPP), a selective inhibitor of heme oxygenase-1(HO-1). Taken together, these findings demonstrated that Bach1 promoted oxidative stress and ferroptosis through suppressing the expression of HO-1. Therefore, Bach1 may present as a promising new therapeutic target for the prevention and early intervention of DOX-induced cardiotoxicity.
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高影响因子
FREE RADICAL BIOLOGY AND MEDICINE
·
2018
·
IF 6.02
Jing Zhao,Jingjing Du,Yang Pan,Tingting Chen,Lihui Zhao,Yanmeng Zhu,Yingfu Chen,Yuyang Zheng,Yu Liu,Lihua Sun,Pengzhou Hang,Zhimin Du
Brain-derived neurotrophic factor (BDNF)/tropomyosin-related receptor kinase B (TrkB) pathway has been revealed as a novel therapeutic target for several neurological diseases . Recently, small-molecule TrkB agonist 7,8-dihydroxyflavone (7,8-DHF) has received considerable attention as a novel potential candidate for the treatment of various BDNF-implicated human disorders. However, its roles in cardiac diseases are not fully understood. Here, the present study aimed to clarify the effects and mechanisms of 7,8-DHF on doxorubicin (Dox)-induced cardiotoxicity . Kunming mice and H9c2 cells were employed to investigate the functional role of 7,8-DHF both in vivo and in vitro. 7,8-DHF markedly increased cell viability and reduced cell death of Dox-treated cells. Meanwhile, 7,8-DHF significantly increased mitochondrial respiration , membrane potential, and optic atrophy 1 (OPA1) protein expression . 7,8-DHF improved cardiac function and attenuated cardiac injury in Dox mice model. Expression of AMP-activated protein kinase (AMPK) and signal transducers and activators of transcription 3 (STAT3) was restored by 7,8-DHF. Furthermore, the protective role of 7,8-DHF was abolished by ANA-12 (a specific antagonist of TrkB). In elucidating the molecular mechanism, the phosphorylation of Akt was significantly increased while extracellular regulated protein kinase (ERK) was decreased after 7,8-DHF treatment. The regulatory effects of 7,8-DHF on STAT3 and AMPK was reversed by Akt inhibitor . In summary, 7,8-DHF attenuated Dox-induced cardiotoxicity by activating Akt and increasing mitochondrial oxidative phosphorylation and thereby regulating STAT3, AMPK, and ERK signals. The present study enhanced current understanding of TrkB receptor in the cardiovascular system and provided a novel target for prevention and treatment of heart diseases.
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Journal of Materials Chemistry B
·
2014
·Vol. 2
·期 30
·4901-4910
·
IF 0
Wenjie Li,Jing Shi,Chun Zhang,Min Li,Lu Gan,Huibi Xu,Xiangliang Yang
The overexpression of thioredoxin (Trx) 1 is one of the mechanisms for drug resistance in hepatocellular carcinoma (HCC) treatment. The co-delivery of drugs and a short hairpin RNA (shRNA) against Trx1 to silence its expression might provide a promising approach to improve drug sensitivity to chemotherapeutic agents. In this paper, cationic liposomes containing gemini surfactants, soybean lecithin and DOPE were firstly constructed as gene transfection carriers. The length and symmetrical degree of aliphatic chains of gemini surfactants were found to affect gene transfection efficiency of cationic liposomes. Cationic liposome containing gemini surfactants with symmetrical C16 aliphatic chains (L16-2-16) showed the highest transfection efficiency in HCC Bel7402 cells and also displayed the strongest DNA condensation capacity and the highest cellular uptake. Folic acid (FA) targeting further enhanced the transfection efficiency of L16-2-16 by binding to the folate receptor (FR) in FR-overexpressing Bel7402 cells and lipid raft/caveolae-dependent endocytosis might be involved in FA-L16-2-16-mediated gene delivery. Then the multifunctional co-delivery system for doxorubicin (DOX) and Trx1 shRNA was developed via electrostatic interactions between the FA-L16-2-16 and Trx1 shRNA/DOX complex. Co-delivery of Trx1 shRNA and DOX by FA-L16-2-16 inhibited the cell viability and induced apoptosis of Bel7402 cells more efficiently than co-delivery of control shRNA and DOX. The system for co-delivering DOX and Trx1 shRNA could simultaneously achieve gene transfection and drug release in the same cell and increase the intracellular as well as intranuclear DOX concentrations. These results demonstrated that gemini surfactant-based cationic liposomes were promising carriers for the co-delivery of nucleic acids and chemotherapeutic agents to sensitize HCC chemotherapy.
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Molecular Medicine Reports
·
2016
·Vol. 14
·期 3
·2853-2859
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IF 1.559
Feng Ding,Tianfeng Liu,Nina Yu,Shihong Li,Xiaofei Zhang,Guanghong Zheng,Chunming Lv,Kai Mou,Jia Xu,Bo Li,Surong Wang,Haibo Song
Nitidine chloride (NC) exhibits anti-tumor properties in various types of tumor. However, to the best of our knowledge there is no previous evidence of NC involvement in the apoptosis or proliferation of ovarian cancer cells and the underlying molecular mechanisms. The present study aimed to investigate the influence of NC on the viability and apoptosis of ovarian cancer cells and the synergistic effect NC and doxorubicin (DOX) may have on ovarian cancer cells. The viability and proliferation of ovarian cancer cells were examined using a methyl thiazolyl tetrazolium assay and 3H-thymidine incorporation assay. The apoptotic rate of ovarian cancer cells was detected by flow cytometry. The expression of apoptosis‑associated proteins and Akt serine/threonine kinase 1 (Akt) were determined by western blot analysis following NC treatment. The inhibitory effect of NC on the proliferation of ovarian cancer cells was demonstrated in a time and dose‑dependent manner. The pro-apoptotic effect of NC on ovarian cancer cells was also observed. It was determined that NC significantly downregulated the protein expression levels of B‑cell CLL/lymphoma 2 (Bcl-2) and upregulated the expression of Bcl‑2‑associated X protein, p53, caspase‑3 and ‑9. NC suppressed Akt phosphorylation. Additionally, the present study demonstrated that the effect of NC on the proliferation and apoptosis of ovarian cancer cells was Akt‑dependent by using the phosphatidylinositol-4,5-bisphosphate 3-kinase/Akt signaling pathway inhibitor, LY294002. NC exhibited a synergistic inhibitory effect on the viability of ovarian cancer cells when combined with DOX. The current study demonstrated that NC inhibited the proliferation and induced the apoptosis of ovarian cancer cells via the Akt signaling pathway and highlighted its potential clinical application for the treatment of ovarian cancer.
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高影响因子
NANOTECHNOLOGY
·
2022
·Vol. 34
·期 6
·065101
·
IF 3.953
Le He,Yuting He,Bin Chi,Mingyue Xu,Qian Song,Tingting Yang,Ling Li,Jing Wang
Fe3+ and 2-methylimidazole were selected to prepare tumor microenvironment targeted and regulated multifunctional drug carrier Fe-MOFs. The fact that Doxorubicin hydrochloride (DOX·HCl) release climbed 70% from 25% upon regulating the pH from 7.4 to 5.8 proved the pH responsive drug release of Fe-MOFs. Hydroxyl radicals (·OH) analysis proved that Fe-MOFs only generated hydroxyl radicals at pH 5.8, and dissolved oxygen performance showed the O2 was produced during the process, which was expected to regulate hypoxia in tumor cells to increase anticancer effect. Cell viability experiments proved the selectivity of Fe-MOFs and the excellent performance of synergy therapy of DOX·HCl and hydroxyl radicals. In vivo magnetic resonance imaging experiments demonstrated excellent performance of positive images. All experiments showed that Fe-MOFs can be used for image-guided collaborative treatment to improve treatment efficiency and reduce side effects.
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MOLECULAR PHARMACEUTICS
·
2021
·
IF 4.939
Xiaoxia Yang,Pengfei Shang,Jianbo Ji,Christina Malichewe,Zhiyin Yao,Jing Liao,Dandan Du,Chao Sun,Lei Wang,Ya-jie Tang,Xiuli Guo
In this study, a chitosan-based, self-assembled nanosystem that codelivered microRNA34a (miR34a) and doxorubicin (Dox) with hyaluronic acid (HA) modification (named CCmDH NPs) was developed to reverse the resistance of breast cancer (BCa) cells to Dox. The CCmDH NPs had a diameter of 180 ± 8.3 nm and a ζ potential of 16.5 mV with a slow-release effect for 96 h. The codelivery system could protect miR34a from nuclease and serum degradation and transport miR34a and Dox into drug-resistant MCF-7/A cells. In addition, the CCmDH NPs could inhibit proliferation and promote apoptosis by regulating the protein expression of B-cell lymphoma-2 (Bcl-2) and poly(ADP-ribose) polymerase (PARP) and inhibit invasion, metastasis, and adhesion by regulating E-cadherin, N-cadherin, MMP2, CD44, and Snail molecules. The CCmDH NPs induced a 73.7% tumor reduction in xenograft tumor growth in nude mice in vivo. This study provides evidence for the anticancer activity of CCmDH NPs carrying Dox and miR34a in BCa, especially metastatic Dox-resistant BCa models.
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RSC Advances
·
2021
·Vol. 11
·期 15
·9021-9028
·
IF 3.361
Meifang Wang,Jing Lin,Jiawei Gong,Mingchen Ma,Hongliang Tang,Jiyang Liu,Fei Yan
Direct and accurate detection of doxorubicin (DOX) in unprocessed human whole blood is of vital importance in medical diagnosis and monitoring. In this work, we demonstrate the utilization of electrochemically pretreated glassy carbon electrodes (p-GCE) modified with vertically-ordered mesoporous silica films (VMSF) for rapid and sensitive electrochemical detection of DOX. The electrochemically pretreated process is a simple, cost-effective and environmentally friendly approach for improving interface catalytic properties and introducing oxygen-containing groups into the GCE surface, which could be suitable for stably growing VMSF without any adhesive layer simultaneously retaining the underlying electrode activity. Benefiting from the highly sensitive electrode substrate of p-GCE and electrostatic preconcentration effect of VMSF, the present VMSF/p-GCE sensor was able to determine DOX with an ultrahigh sensitivity (23.94 μA μM−1) and a relatively low limit of detection (0.2 nM) and a rather wide linear range (0.5 nM to 23 μM). Furthermore, direct and reliable electrochemical detection of DOX in human whole blood without complicated sample pretreatments was achieved owing to the excellent anti-fouling and anti-interference ability of VMSF.
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MACROMOLECULAR BIOSCIENCE
·
2021
·Vol. 21
·期 6
·2100049
·
IF 4.979
Yingge Shi,Dong Li,Chaoliang He,Xuesi Chen
Combination therapy can be used to enhance the therapeutic response and decrease side effects during cancer treatment. In this study, a system is developed to locally deliver the immune checkpoint blockade antibody targeting programmed death-ligand 1 (anti-PD-L1 or aPD-L1) and doxorubicin (Dox), by an injectable, biocompatible polypeptide hydrogel as a drug depot. The localized and sustained release of Dox after the intratumoral injection of the co-loaded hydrogel induces immunogenic tumor cell death, thus promoting an antitumor immunological response. The tumor inhibitory effect is significantly enhanced by the simultaneous release of aPD-L1 at the tumor site thanks to its action on the inhibition of the PD-1/PD-L1 pathway and restoration of the tumor-killing effect of cytotoxic T cells. Treatment of the B16F10 melanoma model with the aPD-L1 and Dox co-loaded hydrogel leads to a remarkable inhibition of tumor progression and prolongation of animal survival.
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Nanoscale
·
2020
·Vol. 12
·期 4
·2673-2685
·
IF 6.895
Yang Li,Yimin Niu,Jianhua Zhu,Cuicui Gao,Qunwei Xu,Zhiyu He,Dawei Chen,Ming Xu,Yang Liu
Legumain enzyme is a well-conserved lysosomal cysteine protease and is over-expressed in many tumor cells and tumor stromal cells and exhibits higher protease activity under acidic conditions, such as in lysosomes and endosomes. Legumain enzyme-triggered drug delivery systems have demonstrated potential therapeutic values in cancer targeted therapy. To realize a more efficient delivery of anticancer therapeutic agents, we herein report a legumain/pH dual-responsive drug delivery system for enhancing site-specific controlled release of antitumor drugs. The carrier (named “DS-NA”) is a hybrid vector constituting PEG-b-PBLA polymers, pH-responsive OAPI polymers, and legumain-sensitive peptide-doxorubicin prodrug decorated fluorescent carbon dots (CDs-C9-AANL-DOX). In tumor cells, DS-NA could disassemble rapidly in acidic environments, and then release doxorubicin through legumain digestion. Except as a drug vector, the drug release process from DS-NA could also be dynamically monitored by CLSM as the DOX was released from the surface of CDs through the AANL peptide linker digested by legumain, then transferred into the cell nucleus and exerted cytotoxicity, while the CDs themselves remained in the cytoplasm. As a control, the CDs-C9-DOX, which did not contain the AANL peptide linker, also still resided in the cytoplasm. Furthermore, in vivo studies show that DS-NA had a stronger inhibitory effect on tumor tissue with attenuated side effects to normal tissues than control nanoparticles or free drugs, which may be due to comprehensive effects including pH/legumain dual-triggered drug release, long blood circulation periods, and EPR effects. Together, a combination strategy of acid sensitivity and legumain enzyme sensitivity used for site-specific controlled release of drugs provides a novel method for enhanced and precise antitumor chemotherapy.
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International Journal of Nanomedicine
·
2023
·
IF 8
Wenbo Wu,Xiaoli Yu,Jiaxiang Sun,Yuanyuan Han,Yuanye Ma,Guoqing Zhang,Qingming Ma,Qiang Li,Hongfei Xiang
Background As a broad-spectrum antitumorigenic agent, doxorubicin (DOX) is commonly used as a chemotherapeutic drug for treating osteosarcoma (OS). Still, it is associated with significant cell toxicity and ineffective drug delivery, whereas the zeolite imidazolate framework is extensively applied in the biomedical field as a carrier owing to its favorable biocompatibility, high porosity, and pH-responsiveness. Therefore, we need to develop a drug delivery platform that can effectively increase the antitumorigenic effect of the loaded drug and concurrently minimize drug toxicity.Methods In this study, a Fe3O4@ZIF-8 nanocomposite carrier was prepared with ZIF-8 as the shell and encapsulated with Fe3O4 by loading DOX to form DOX- Fe3O4@ZIF-8 (DFZ) drug-loaded magnetic nanoparticles. Then, we characterized and analyzed the morphology, particle size, and characteristics of Fe3O4@ZIF-8 and DFZ by TEM, SEM, and Malvern. Moreover, we examined the inhibitory effects of DFZ in vitro and in vivo. Meanwhile, we established a tumor-bearing mouse model, evaluating its tumor-targeting by external magnetic field guidance.Results DFZ nanoparticles possessed have a size of ~110 nm, with an encapsulation rate of 21% and pH responsiveness. DFZ exerted a superior cytostatic effect and apoptosis rate on K7M2 cells in vitro compared to DOX(p<0.01). In animal experiments, DFZ offers up to 67% tumor inhibition and has shown a superior ability to induce apoptosis than DOX alone in TUNEL results(p<0.01). Tumor-targeting experiments have validated that DFZ can be effectively accumulated in the tumor tissue and enhance anticancer performance.Conclusion In summary, the DFZ nano-delivery system exhibited a more substantial anti-tumorigenic effect as well as superior active tumor targeting of DOX- Fe3O4@ZIF-8 compared to that of DOX alone in terms of biocompatibility, drug loading capacity, pH-responsiveness, tumor-targeting, and anti-tumorigenic effect, indicating its chemotherapeutic application potential.
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