Acta Biomaterialia
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2025
·
IF 9.6
Sheng Xu,Ziwei Hu,Weihao Zheng,Chaozhen Qin,Xiaoyu Bai,Qinghua Yang,Tao Zeng,Dandan Mo,Bo Zhou,Chun Lu,Xiaomin Chen,Biying Tan,Jinmin Zhao,Li Zheng
Osteosarcoma (OS), a highly malignant primary tumor, poses significant threats. Chemotherapy remains the main treatment approach but is limited by low drug bioavailability, poor permeability, and notable side effects. Herein, a near-infrared light (NIR)-driven and GSH-responsive poly(ethylene glycol)-SS-polystyrene-doxorubicin and platinum nanoparticles (PSPDP) nanomotor, wherein disulfide bonds served as GSH sponsors and platinum nanoparticles as producers of reactive oxygen species (ROS) to induce cell apoptosis, combined with NIR-driven propulsion to enhance the inhibitory effect of encapsulated doxorubicin (DOX). The results demonstrated that the PSPDP nanomotor can be effectively driven due to its good photothermal properties, with its movement speed increased 2.10 times under NIR laser exposure. Additionally, the efficiency of DOX release increased with the increase in GSH concentration, demonstrating favorable GSH responsiveness. Pt-NPs also exhibited good photothermal properties, enabling self-thermophoresis to drive. Minimal cytotoxic effects of PSPDP were observed on a series of cell lines compared with DOX solution and Pt-NPs. Notably, the Pt-NPs generated a significant amount of ROS, synergistically enhancing the therapeutic effect of DOX, as evidenced by a 5.53-fold increase in OS cell growth inhibition and evident osteosarcoma growth inhibition in the nude mice model. Thus, the NIR-driven, localized, and low-toxic nanomotor may offer a promising therapeutic strategy for OS intervention. Statement of significance Enhancing drug penetration efficiency and developing delivery systems that respond to the tumor microenvironment to release drugs are effective strategies for treating osteosarcoma (OS). Here, a near-infrared (NIR) light-driven and glutathione (GSH)-responsive nanomotor, integrating poly(ethylene glycol)-SS-polystyrene-doxorubicin and platinum nanoparticles (PSPDP), was produced and used for OS treatment. This PSPDP nanomotor exhibits significant advancements in photothermal activation and self-thermophoresis, enabling a 2.10-fold increase in movement speed under NIR exposure. Such enhanced motility improves the localized delivery and controlled release of doxorubicin, thus increasing drug bioavailability and minimizing systemic toxicity. Additionally, the nanomotor's ability to generate reactive oxygen species significantly amplifies its therapeutic impact, evidenced by a remarkable 5.53-fold increase in tumor growth inhibition. These features make the PSPDP nanomotor a promising candidate for effective and targeted OS treatment strategies.
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高影响因子
INTERNATIONAL JOURNAL OF PHARMACEUTICS
·
2024
·
IF 5.3
Chenyu Cao,Yifei Li,Fangzhou Shi,Shanshan Jiang,Yutong Li,Leilei Yang,Xinyi Zhou,Yuqiong Gao,Feiyan Tang,Huan Li,Shulan Han,Zhuo Yu,Yifang Zou,Jianfeng Guo
Doxorubicin (DOX) is a chemotherapy drug used for hepatocellular carcinoma (HCC) treatment, but its effectiveness can be dramatically dampened by cancer cell chemoresistance. Signal transducer and activator of transcription 3 (STAT3) is implicated with drug resistance in a range of cancers (e.g., HCC), and the STAT3 inhibition can reverse the resistance of cancer cells to chemotherapeutic drugs. In the present study, a combination regimen to improve the efficiency of DOX was provided via the STAT3 blockade using plumbagin (PLB). A poly(lactic-co-glycolic acid) decorated by polyethylene glycol and aminoethyl anisamide was produced in the present study with the hope of generating the nanoparticles for co-delivery of DOX and PLB. The resulting co-formulation suppressed the STAT3 activity and achieved the synergistic chemotherapy, which led to tumor inhibition in the mice with subcutaneous DOX-resistant HCC, without causing any toxicity. The present study reveals the synergism of DOX and PLB, and demonstrates a promising combinatorial approach for treating HCC.
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Nanomedicine
·
2018
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IF 5.005
Huanan Li,Deping Zeng,Zhenyu Wang,Liaoqiong Fang,Faqi Li,Zhibiao Wang
Aim: To build up a combined therapy strategy to address limitations of the enhanced permeability and retention (EPR) effect and improve the efficiency of tumor therapy. Materials & methods: A pH-sensitive nanocomplex for co-delivery of doxorubicin (DOX) and all-trans retinoic acid (ATRA) was developed based on nanodiamonds (DOX/ATRA-NDs) to enhance intracellular retention of drugs. Meanwhile, ultrasound was employed to enhance tumor vascular penetration of DOX-ATRA-NDs. Results: The distribution of DOX/ATRA-NDs in the tumor tissues increased threefold when ultrasound was applied at 1 MHz and 0.6 W/cm2. Comparing with unmodified chemotherapeutics, the combined therapy induced more tumor cells apoptosis and greater tumor growth inhibition in both liver and breast tumor models. Conclusion: DOX-ATRA-NDs demonstrate great potential in clinical applications.
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DRUG RESISTANCE UPDATES
·
2025
·
IF 21.7
Muhammad Zubair Saleem,Ruyi Huang,Yingying Huang,Xin Guo,Yang Liu,Miao Gao,Yinjuan Fan,Zhe-Sheng Chen,Zun-Fu Ke,Shengnan Ye,Jianhua Xu
Aims TRAP1 is involved in metabolic reprogramming and promotes drug resistance. We aimed to explore whether a novel HSP90 inhibitor, C210, overcomes doxorubicin (DOX) resistance of quiescent breast cancer cells by targeting TRAP1. Methods Breast cancer cells were induced to quiescence by hypoxia and low glucose. The relationship of cell metabolism with HSP90 and TRAP1 was investigated by Western blotting, ECAR, OCR, mitochondrial complex activity, and proteomic analysis. The targets of C210 and their functions were analyzed by SPR and immunoprecipitation. The antitumor effect in vivo was investigated with mouse tumor model. Results In hypoxia and glucose deprivation, breast cancer cells exhibited elevated TRAP1 and an OXPHOS-enhanced quiescent phenotype. These cells were highly resistant to DOX but more sensitive to C210. C210 disrupted TRAP1's interaction with OXPHOS-associated client proteins, prompting proteasome-dependent degradation of these proteins, thereby reducing OCR, mitochondrial ATP production and resulting in selective elimination of the quiescent cancer cells by inducing mitochondrial apoptosis which could be reversed by exogenous ATP. Moreover, C210 targeted glycolytic, amino acid, and β-oxidation-associated proteome. C210 demonstrated promising in vivo anticancer efficacy which was particularly related to OXPHOS inhibition. Conclusions C210 eliminates DOX-resistant quiescent breast cancer cells by targeting TRAP1-dependent bioenergetics.
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RSC Advances
·
2019
·Vol. 9
·期 23
·13026-13032
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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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高影响因子
Nanoscale
·
2020
·Vol. 12
·期 25
·13801-13810
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IF 6.895
Xia Meng,Yurui Xu,Qiangbing Lu,Lei Sun,Xueying An,Jikang Zhang,Jianmei Chen,Ya Gao,Yu Zhang,Xinghai Ning
Lactic acidosis is one of the key characteristics of the tumor microenvironment (TME), and plays a critical role in therapy resistance, making it an attractive target for enhancing anticancer treatment. However, no effective systems exhibit the ability to selectively neutralize tumor lactic acidosis in a controlled manner. Here, we have developed novel ultrasound-responsive alkaline nanorobots (AN-DSP), composed of PLGA nanoparticles containing doxorubicin (DOX), sodium carbonate (Na2CO3) and perfluorocarbon (PFC), for recovering from lactic acidosis-mediated drug resistance. AN-DSP exhibit sensitive response to ultrasound stimulation, and rapidly release Na2CO3 to neutralize lactic acidosis, consequently enhancing DOX susceptibility in vitro and in vivo. Particularly, our nanorobots autonomously accumulate in tumors by an enhanced permeability and retention effect, and can specifically disrupt the tumor acidic microenvironment in response to external ultrasonic powering, resulting in the inhibition of tumor growth with minimal adverse effects. Therefore, AN-DSP represent a promising approach for selectively overcoming tumor lactic acidosis induced therapeutic resistance.
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MOLECULAR PHARMACEUTICS
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2018
·
IF 4.556
Yijia Yin,Qian Hu,Chenfeng Xu,Qi Qiao,Xianya Qin,Qingle Song,Yang Peng,Yongdan Zhao,Zhiping Zhang
A dual-sensitive nanoparticle delivery system was constructed by incorporating an acid sensitive hydrazone linker into thermosensitive nanoparticles (TSNs) for co-encapsulating doxorubicin (DOX) and interferon γ (IFNγ) and to realize the co-delivery of chemotherapy and immunotherapy agents against melanoma. DOX, a chemotherapeutic drug, was conjugated to TSNs by a pH-sensitive chemical bond, and IFNγ, a potent immune-modulator, was absorbed into TSNs through the thermosensitivity and electrostatics of nanoparticles. Consequently, the dual sensitive drug-loaded TSN delivery systems were successfully built and showed an obvious core–shell structure, good encapsulation efficiency of drugs, sustained and sensitive drug release, prolonged circulation time, as well as excellent synergistic antitumor efficiency against B16F10 tumor bearing mice. Moreover, the combinational antitumor immune responses of hydrazone bearing DOX/IFNγ-TSN (hyd) were strengthened by activating Th1-type CD4+ T cells, cytotoxic T lymphocytes, and natural killer cells, downregulating the expression levels of immunosuppressive cytokines, such as IL10 and TGFβ, and upregulating the secretion of IL2 and TNFα. Taken together, the multifunctional TSNs system provides a promising strategy for multiple drugs co-delivery with distinct properties.
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高影响因子
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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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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SENSORS AND ACTUATORS B-CHEMICAL
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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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CARDIOVASCULAR DRUGS AND THERAPY
·
2025
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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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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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