BIOMACROMOLECULES
·
2016
·
IF 5.583
Yanjuan Wu,Dongfang Zhou,Qingfei Zhang,Zhigang Xie,Xuesi Chen,Xiabin Jing,Yubin Huang
A tumor is a complicated system, and tumor cells are typically heterogeneous in many aspects. Polymeric drug delivery nanocarriers sensitive to a single type of biosignals may not release cargos effectively in all tumor cells, leading to low therapeutic efficacy. To address the challenges, here, we demonstrated a pH/reduction dual-sensitive charge-conversional polymeric prodrug strategy for efficient codelivery. Reduction-sensitive disulfide group and acid-labile anticancer drug (demethylcantharidin, DMC)-conjugated β-carboxylic amide group were repeatedly and regularly introduced into copolymer chain simultaneously via facile CuAAC click polymerization. The obtained multifunctional polymeric prodrug P(DMC), mPEG-b-poly(disulfide-alt-demethylcantharidin)-b-mPEG was further utilized for DOX encapsulation. Under tumor tissue/cell microenvironments (pH 6.5 and 10 mM GSH), the DOX-loaded polymeric prodrug nanoparticles (P(DMC)@DOX NPs) performed surface negative-to-positive charge conversion and accelerated/sufficient release of DMC and DOX. The remarkably enhanced cellular internalization and cytotoxicity in vitro, especially against DOX-resistant SMMC-7721 cells, were demonstrated. P(DMC)@DOX NPs in vivo also exhibited higher tumor accumulation and improved antitumor efficiency compared to P(SA)@DOX NPs with one drug and without charge-conversion ability. The desired multifunctional polymeric prodrug strategy brings a new opportunity for cancer chemotherapy.
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RSC Advances
·
2019
·Vol. 9
·期 23
·13026-13032
·
IF 3.049
Linlin Fan,Xuyang Sun,Xuelin Wang,Hongzhang Wang,Jing Liu
Liquid metals (LMs) have recently emerged as a new class of promising multifunctional materials with attractive properties. They have excellent photothermal conversion efficiency, generating heat under near-infrared (NIR) laser irradiation. This work reports encapsulating LM droplets into poly(NIPAm-co-MBA) hydrogels (PNM) to achieve nanodispersed liquid metals in bulk polymeric hydrogels for NIR laser-responsive materials. LM droplets (∼530 nm) are produced by dispersing an alloy of gallium and indium (EGaIn) into glycerol. The LM-loaded PNM hydrogels (PNM/LM) exhibited excellent thermal-/NIR laser-responsive ability. In a water bath, the weight of the PNM/LM can decrease 92% at 50 °C. And the volume of PNM/LM can decrease 62% under NIR laser irradiation for 12 min. Because of its thermal-/NIR laser-responsive ability and porous three-dimensional (3D) networks, PNM/LM is very suitable for use as a drug carrier. We also prepared doxorubicin (DOX)-loaded PNM/LM hydrogels (PNM/LM/DOX) and demonstrated that the PNM/LM/DOX hydrogel can generate heat and raise its temperature under NIR laser irradiation. When the temperature becomes higher than the lower critical solution temperature (LCST), such a hydrogel would shrink immediately and extrude the DOX encapsulated in its networks simultaneously, then complete the controlled release of the pre-loaded drug. Further, an in vitro cytotoxicity test indicated the biocompatibility and feasibility as a chemophotothermal synergistic therapeutic of the present hydrogel. This NIR laser-responsive hydrogel fully exhibits its superiority as a drug carrier which promises great potential in future targeted controlled drug release.
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JOURNAL OF NANOSCIENCE AND NANOTECHNOLOGY
·
2019
·Vol. 19
·期 9
·5456-5462
·
IF 1.093
Jie Liyong,Lang Dan,Kang Xuqi,Yang Zhixin,Du Yongzhong,Ying Xiaoying
The magnetic resonance imaging diagnosis and high-efficiency tumor targeting treatment are of notable importance for cancer therapy. In this study, starch-octanoic acid (ST-OA) micelles were successfully prepared to co-encapsulate the anti-tumor drug doxorubicin (DOX) and superparamagnetic
iron oxide nanoparticles (SPIONs), taking advantage of the hydrophobic core of the core–shell micellar structure. Size distribution, morphology and in vitro release behaviors of micelles were investigated. In addition, magnetic properties and the anti-tumor theranostic performance
were confirmed by conducting the cellular uptake, in vivo imaging and anti-tumor activity experiments. Therefore, co-encapsulation and specific delivery of the chemotherapeutic drug and contrast agent into tumor cells can realize the diagnosis and treatment of malignant tumor at the
same time.
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RSC Advances
·
2016
·Vol. 6
·期 31
·26280-26287
·
IF 3.289
Binbin Li,Heng Liu,Chuanbin Sun,Zeeshan Ahmad,Zhaohui Ren,Xiang Li,Gaorong Han
The investigation of nano-carriers with controllable and trackable drug release kinetics has attracted worldwide attention for new tumor theranostic strategies with catabatic side effects. Herein, a range of monodispersed core–shell structured photoluminescent SrTiO3:Yb3+,Er3+@mSiO2 nanoparticles were designed and synthesized. The surfactant cetyltrimethylammonium bromide (CTAB) was used to vary the microstructure of the mesoporous SiO2 shell. The specific surface area and pore volume increase proportionally with the content of CTAB. Consequently, the doxorubicin (DOX) loading capacity increases, and the drug release kinetics possesses a sustained behaviour. More importantly, the DOX release kinetics was found to correspond well to the evolution of the up-conversion luminescence (UCL) phenomenon. More rapid drug release induces more rapid photoluminescence enhancement, and vice versa. This study has therefore been anticipated to suggest another promising multifunctional drug delivery platform for advanced chemotherapies.
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INTERNATIONAL JOURNAL OF BIOCHEMISTRY & CELL BIOLOGY
·
2024
·
IF 3.4
Jiawen Chen,Xiaozhi Xu,Yuru Shao,Xiaohong Bian,Ruiyan Li,Yubin Zhang,Yibei Xiao,Meiling Lu,Qizhou jiang,Yuan Zeng,Fangrong Yan,Junmei Ye,Zhe Li
Doxorubicin (DOX), a widely used chemotherapy agent in cancer treatment, encounters limitations in clinical efficacy due to associated cardiotoxicity. This study aims to explore the role of AKT serine/threonine kinase 2 (AKT2) in mitigating DOX-induced oxidative stress within the heart through both intracellular and extracellular signaling pathways. Utilizing AKT2 knockout (KO) and NRF2 KO murine models, alongside neonatal rat cardiomyocytes (NRCMs), we systematically investigate the impact of AKT2 deficiency on DOX-induced cardiac injury. Our findings reveal that DOX administration induces significant oxidative stress, a primary contributor to cardiac injury. Importantly, Akt2 deficiency exhibits a protective effect by alleviating DOX-induced oxidative stress. Mechanistically, Akt2 deficiency facilitates nuclear translocation of NRF2, thereby suppressing intracellular oxidative stress by promoting the expression of antioxidant genes. Furthermore, We also observed that AKT2 inhibition facilitates superoxide dismutase 2 (SOD2) expression both inside macrophages and SOD2 secretion to the extracellular matrix, which is involved in lowering oxidative stress in cardiomyocytes upon DOX stimulation. The present study underscores the important role of AKT2 in mitigating DOX-induced oxidative stress through both intracellular and extracellular signaling pathways. Additionally, our findings propose promising therapeutic strategies for addressing DOX-induced cardiomyopathy in clinic.
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Small Methods
·
2025
·
IF 9.1
Wenbo Yin,Zonghang Liu,Shangjie An,Tao Song,Yue Wang,Xiue Jiang
Doxorubicin (DOX) is a clinically approved chemotherapeutic agent that exerts its cytotoxicity through DNA intercalation and topoisomerase II inhibition. However, its redox-based mechanism remains underexplored. Here, it is revealed that DOX specifically binds to the heme center of cytochrome P450 (CYP450) enzymes via its quinone moiety, enabling electron transfer that catalyzes molecular oxygen into superoxide anions (O 2 •− ). To enhance this process, mesoporous polydopamine (mPDA) is introduced as an electron-rich scaffold, amplifying electron flow to DOX. Furthermore, L-arginine (L-Arg) is co-delivered to supply nitric oxide (NO), which reacts with O 2 •− to generate peroxynitrite (ONOO − ), a stable, highly cytotoxic ROS. ONOO − further activates matrix metalloproteinase (MMP), promoting extracellular matrix degradation and facilitating drug/oxygen penetration. Moreover, the system enables multimodal tumor therapy by integrating DOX-based chemotherapy, nitric oxide (NO) gas therapy, and mPDA-mediated photothermal therapy. This work unveils a novel DOX-CYP450 electron transfer mechanism and establishes a synergistic therapeutic paradigm to overcome tumor microenvironmental barriers and enhance treatment efficacy.
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CARDIOVASCULAR DRUGS AND THERAPY
·
2025
·
IF 3.1
Huang Jie,Hou Xingyuan,Zhou Ni,Su Nan,Wei Shanshan,Yang Yuanying,Sun Taoli,Li Guangdi,Li Wenqun,Zhang Bikui
Purpose Doxorubicin (Dox) is a classic anthracycline chemotherapy drug with cause cumulative and dose-dependent cardiotoxicity. This study aimed to investigate the potential role and molecular mechanism of phenylacetylglutamine (PAGln), a novel gut microbiota metabolite, in Dox-induced cardiotoxicity (DIC). Methods DIC models were established in vivo and in vitro, and a series of experiments were performed to verify the cardioprotective effect of PAGln. RNA sequencing (RNA-seq) was employed to explore the mechanism of PAGln in DIC. Subsequently, the differentially expressed genes (DEGs) were subjected to comprehensive analysis using diverse public databases, and RT-PCR was used to confirm the expression levels of the candidate genes. Finally, molecular docking techniques were used for validation. Results PAGln effectively prevented both in vivo and in vitro Dox-induced myocardial injury and cell apoptosis. RNA-seq results showed that 40 genes were up-regulated and 54 down-regulated in the Dox group compared to the Con group, displaying opposite changes in the Dox + PAGln group. Enrichment analysis highlighted several mechanisms by which PAGln alleviated Dox-induced cardiotoxicity, including the lipid metabolic process, calcium-mediated signaling, positive regulation of store-operated calcium channel activity, and hypertrophic cardiomyopathy. In vitro and in vivo experiments confirmed that PAGln treatment could reverse the changes in the expression levels of Klb, Ece2, Nmnat2, Casq1, Pak1, and Apob in Dox. Molecular docking results showed that these genes had good binding activity with PAGln. Conclusions PAGln shows potential in alleviating Dox-induced cardiotoxicity, with Ece2 identified as key regulatory molecules related to endothelial dysfunction.
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CHEMOSPHERE
·
2019
·
IF 5.108
Linglu Gao,Qing He,Jinfeng Xing,Zhiqiang Ge
Doxorubicin (DOX) originated from users’ urine has been an emerging environmental pollutant due to its significant genotoxicity to mankind. Thus, urine source separation is a potential strategy to isolate DOX at a higher concentration and reduce the burden of downstream wastewater treatment . To develop highly efficient, easy separation and retrievable materials for individual patient to conveniently remove DOX from own urine, magnetic Cu 3 (PO 4 ) 2 nanoflowers were prepared through anchoring amino-functionalized magnetic nanoparticles on the Cu 3 (PO 4 ) 2 nanoflowers. Characterizations revealed the magnetic nanoflowers were spherical in shape with a mean size of 15 μm, and porous and hierarchical in structure. Magnetic nanoparticles located the surface of petals. Multibatch experiments were performed to assess the removal performance of DOX from aqueous solution. The magnetic nanoflowers exhibited excellent removal efficiency of DOX under weakly alkaline condition at ambient temperature. Linear and non-linear analyses were carried out to compare the best fitting kinetics and isotherms. Sorption kinetic data best fitted the pseudo-second order model. The Freundlich isotherm explained equilibrium sorption data with R 2 = 0.993 higher than that for the Langmuir isotherm. When the pH of synthetic urine was adjusted to weakly alkaline (pH 8.0–9.0), over 95% of DOX (20 mg L −1 ) was removed by a little of magnetic nanoflowers (50 mg L −1 ) within 5 min. Meanwhile, the magnetic nanoflowers could be easily separated and recovered from the synthetic urine by a magnet. So, for individual urine source separation strategy, the magnetic nanoflower seems to be an efficient, convenient and inexpensive approach to remove DOX from human urine.
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Journal of the Taiwan Institute of Chemical Engineers
·
2024
·
IF 5.5
Xiao Duan,Qiang Wang,Wenfeng Che,Ting Li,Ke Zhang,Lingna Han,Lihua Song,Wei Guo
Background Doxorubicin (Dox) is a potent anticancer drug with severe side effects to normal tissues. To fabricate a nanomedicine with Dox is a better method to address the side effects of Dox in normal tissues. However, nanomedicines with unapproved materials could not be easily applied in clinic, hence, a nanomedicine fabricated by endogenous materials is a potential method to increase the possibility of clinical application. Methods In this study, a redox-responsive nanomedicine with clinical-applied anticancer of Dox and endogenous molecule of l -glutathione oxidized (GSSG) was prepared for cancer therapy. : The carboxyl and amino groups in l -glutathione oxidized can be reacted itself to form the poly- l -glutathione oxidized peptide-like polymer. Meanwhile, the Dox were conjugated in poly- l -glutathione oxidized polymer by amnio group in Dox and the structure of Dox-conjugated poly- l -glutathione oxidized polymer (Dox-Poly GSSG) was confirmed by FT-IR, NMR and MALDIT-TOF. Afterward, the drug loading of Dox (22 %) in poly-GSSG was measured by UV–vis and the accumulative Dox release rate of Dox-Poly GSSG is 46 % in 5 mg/mL reduced glutathione (GSH) environment at 72 h The size stability of Dox-Poly GSSG in PBS and PBS with GSH was evaluated by dynamic laser scatter (DLS) and transmit emission microscopy (TEM). Furthermore, cell viabilities of Dox-Poly GSSG were similar with free Dox evaluated by CCK-8 assay and flow cytometry experiment, respectively. The distribution of Dox-Poly GSSG in nuclei and tumor tissues was evaluated by Confocal laser scanning microscope and in vivo imaging system, respectively. Significant Findings The drug release results showed that the Dox could be controllable released in high concentration of GSH in tumor tissues. The tumor inhibition, H&E and TUNEL experiments showed that the Dox-Poly GSSG group can significantly inhibit the tumor growth compared to saline group and avoid major side effects to normal tissues compared to free Dox. This redox-responsive nanomedicine with clinical-applied anticancer of Dox and endogenous molecule of GSSG is a potential candidate for clinical application.
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SENSORS AND ACTUATORS B-CHEMICAL
·
2025
·
IF 7.7
Da Jun Wu,Li Ya Liang,Yichen Shi,Ya Ting Gao,Shuai Chang,Jian Lv,Ruo Can Qian,Da Wei Li,Bin Bin Chen
Phosphorescent sensing probes have attracted considerable attention due to their ability to eliminate autofluorescence interference in biological samples. However, constructing water-stable phosphorescent materials remains a significant challenge because of water-quenched phosphorescence (phos.) property. Herein, a facile one-step thermal polymerization is proposed to synthesize aluminium/4-chlorobenzoicacid phosphorescent materials (Al/PCBA-PMs). The obtained Al/PCBA-PMs have two phos. emissions at 438 nm and 515 nm, respectively, with a lifetime of 83.67 ms. Importantly, the Al/PCBA-PMs show good water-stable phosphorescent property, and the introduction of water can cause a change in phosphorescent color of Al/PCBA-PMs from blue to green, but which has only a small impact on phosphorescent intensity and lifetime. Furthermore, a system of phos. resonance energy transfer (PhRET) can be constructed where Al/PCBA-PMs act as phosphorescent donors and doxorubicin (DOX) serves as fluorescent acceptors. This PhRET system has a high efficiency of 44.25 %, which can achieve the direct and precise determination of DOX in biological samples with strong autofluorescence, with a linear range of 0 −100 μM. This work proposes a powerful strategy for constructing water-stable phosphorescent probes and develops a new type of PhRET system to achieve precise phosphorescent detection in biological samples.
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FASEB JOURNAL
·
2025
·Vol. 39
·期 24
·e71369
·
IF 4.2
Mengxin Li,Xuanzhong Wang,Jinghui Hong,Xin Guan,Yichang Chen,Hongxu zhou,Xin Wang,Baoling Liang,Xiaochuan Gao,Yuheng Wu,Dong Song
Breast cancer (BC) continues to be a representative malignancy globally, with its inherent heterogeneity and chemotherapy resistance posing significant therapeutic obstacles. Doxorubicin (Dox), a commonly utilized chemotherapeutic agent, is often constrained by dose-dependent toxicities and acquired resistance, which ultimately lead to suboptimal clinical outcomes in numerous BC patients. Co-treatment of Dox with RSL3, a small-molecule compound that inactivates glutathione peroxidase 4 (GPX4), was shown in this study to synergistically inhibit BC cell viability and proliferation at low doses in vitro and in vivo. In vitro tests showed that RSL3 exacerbated Dox-induced cell cycle arrest and apoptosis, markedly potentiating the cytotoxicity of Dox against BC cells. Mechanistically, RSL3 triggered ferroptosis-dependent ROS accumulation, leading to glycolytic impairment characterized by reduced intracellular ATP and pyruvate concentrations levels and downregulation of HKII, PFKP, and PKM2. Supplementation with exogenous sodium pyruvate ameliorated RSL3-induced glycolytic dysfunction, restored the changes in apoptosis-related protein expression caused by RSL3/Dox co-treatment, and reduced RSL3/Dox-induced cell apoptosis. Besides, according to in vivo studies, the combination of RSL3 and Dox further suppressed BC tumor growth without inducing significant adverse effects. On these accounts, RSL3 makes BC cells more sensitive to Dox by inducing glycolytic dysfunction, implying that RSL3/Dox co-treatment could be a viable therapeutic approach for BC patients. Graphical RSL3 Mitigates Doxorubicin Resistance in Breast Cancer via Targeted Disruption of Glycolytic Flux. Co-treatment with RSL3 and doxorubicin (Dox) synergistically inhibits breast cancer growth in vitro and in vivo. RSL3 sensitizes BC cells to Dox by inducing ferroptosis and ROS accumulation, which impairs glycolysis (reducing ATP/pyruvate and downregulating HK2/PFKP/PKM2). This metabolic disruption exacerbates Dox-induced cell cycle arrest and apoptosis. The combination therapy offers enhanced efficacy without significant toxicity, presenting a promising low-dose therapeutic strategy.
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BIOMEDICAL MICRODEVICES
·
2020
·Vol. 22
·期 4
·1-11
·
IF 2.176
Yang Yamin,Liu Sijia,Chen Chunxiao,Huang Haipeng,Tao Ling,Qian Zhiyu,Li Weitao
The advent of microfluidic technologies has enabled a better recapitulation of in vitro tumor model with higher biological relevance over conventional monolayer assays. This work built upon a microfluidic system that supported the spontaneous aggregate formation of tumoral cells under flow-induced dynamic physical forces in a confined microchamber without additional matrix materials. Our findings indicated that fluidic streams significantly modulated the biological and architectural features of human breast adenocarcinoma cell (MCF-7), human hepatocarcinoma cell (HepG2), and human cervix adenocarcinoma cell (HeLa) with cell-type-dependent variation. The microfluidic platform was further integrated with a fluorescence detection and imaging system, allowing for non-invasive monitoring of cellular accumulation and spatial distribution of a chemotherapeutic agent, doxorubicin (DOX). The cytotoxic effects of DOX of various concentrations were determined and compared in MCF-7 cells in conventional two-dimensional (2D) static and microfluidic culture conditions. Dose-dependent response to DOX was noticed in both cultures, whereas tumor micronodules grown in microfluidic devices demonstrated significantly lower sensitivity to DOX at increased concentration. Our platform owns promising potentials as a universal modality for bridging traditional 2D cell cultures and in vivo experimentation for preclinical anticancer drug screening.
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