RSC Advances
·
2020
·Vol. 10
·期 56
·33894-33902
·
IF 3.119
Feng Tian,Chen Xu,Mingyue Xu,Haiqing Gao,Ziyi Xiao,Ling Li,Yingxi Wang
Drug resistance is a major obstacle in cancer treatment, and designing a material that monitors real-time drug release remains a top priority. In this study, metal–organic frameworks doped with lanthanum and thulium were synthesized and then coated with aminated silica to form La/Tm-MOF@d-SiO2 as a drug carrier. Doxorubicin hydrochloride (DOX) was selected as a drug model, and the drug loading and release were investigated. It was found that the release of DOX under acidic conditions reached an optimal level, indicating the pH-responsiveness of La/Tm-MOF@d-SiO2. Under acidic conditions (pH = 5.8), upconversion fluorescence was generated after loading DOX on La/Tm-MOF@d-SiO2. At pH = 5.8, the longer the drug released, the stronger the upconversion fluorescence. It was found that the upconversion fluorescence intensity is directly proportional to the amount of drug released; thus, the real-time monitoring of DOX release in tumor cells can be performed based on the upconversion fluorescence.
✓ 已验证
DOI
高影响因子
Scientific Reports
·
2025
·Vol. 15
·期 1
·40205
·
IF 3.9
Tang Cheng,Zou Yangyang,Meng Hao,Xu Jin,Long Fang,Chen Xiaoli,Xiao Qingling,Su Kelei,Nan Zhang,Guo Yaoyao,Li Chaojuan
To develop excipient-free carrier-free nanoparticles (DE NPs) via self-assembly of doxorubicin (DOX) and emodin (EMO) for enhanced combination chemotherapy against non-small cell lung cancer (NSCLC). DE NPs were fabricated through non-covalent interactions between DOX and EMO using a self-assembly method. The nanoparticles were characterized for morphology, stability, encapsulation efficiency, and cellular uptake. In vitro cytotoxicity and in vivo antitumor efficacy of free drugs (EMO, DOX), DOX/EMO mixture, and DE NPs were evaluated on A549 NSCLC cells. Mechanistic studies explored the role of DE NPs in suppressing efflux pump proteins via modulation of p65 activation and nuclear translocation. DE NPs formed rod-like nanostructures with high encapsulation efficiency (> 90%) and stability. They exhibited enhanced cellular uptake and intracellular drug accumulation compared to free drugs or the mixture. In vitro studies demonstrated significantly stronger cytotoxicity in A549 cells (IC50 reduction of ~ 50%) and a synergistic antitumor effect (combination index < 0.5). In vivo studies further confirmed the superior antitumor efficacy of DE NPs over individual DOX or EMO monotherapy (72.67 ± 7.20% tumor inhibition rate). Mechanistically, DE NPs inhibited p65 activation and nuclear translocation, downregulating efflux pump protein expression and prolonging drug retention in cancer cells. The excipient-free DE NPs provide a promising carrier-free nanomedicine platform for NSCLC treatment, achieving synergistic antitumor efficacy through enhanced drug delivery and suppression of drug resistance mechanisms. This strategy highlights the potential of self-assembled dual-drug nanoparticles to improve therapeutic outcomes in combination.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Pharmaceuticals
·
2025
·Vol. 18
·期 11
·1759
·
IF 4.8
Jing Hong,Fangyu Zhang,Ruizhen Zhang,Hongyang Fu,Dongang Shen,Xinyue Wang,Yuting Yang,Jiamei Wu,Lin Meng,Hongyang Lü,Xiwei Jiang,Yunli Zhao
Background: Doxorubicin (DOX) is a highly effective chemotherapy drug, but its use is limited by dose-dependent cardiotoxicity, driving the search for protective natural products. Although the herb Viscum coloratum (Kom.) Nakai is known for its cardiovascular benefits, the cardioprotective effects and mechanisms of its isolated compound, DHDK, remain unexplored. Methods: The protective effect of DHDK was first evaluated in DOX-injured H9c2 cardiomyocytes. Subsequently, an integrated network toxicology (incorporating DOX-induced toxicity targets and relevant chronic disease pathways such as aging and lipid metabolism) and pharmacology (DHDK) approach identified core targets, which were then refined through Protein–Protein Interaction (PPI) analysis and molecular docking. The underlying mechanism was investigated using lipidomics and validated through a series of in vitro assays, including CCK-8, q-PCR, biochemical tests, and flow cytometry, as well as in an in vivo rat model. Results: DHDK significantly alleviated DOX-induced cardiomyocyte toxicity. Integrated analysis identified 56 intersecting targets, with PPARG confirmed as the primary target via PPI and molecular docking. Lipidomics revealed that DHDK potently attenuated DOX-induced accumulation of pathogenic lipids (e.g., fatty acids, ceramides). Mechanistically, DHDK activated PPARG, which in turn upregulated CPT1B, a key regulator of fatty acid β-oxidation (FAO). This enhanced cell viability, ATP production, and mitochondrial membrane potential while reducing oxidative stress. These protective effects, which were abolished by the inhibition of PPARG or CPT1B, were further validated in vivo. Conclusion: This study demonstrates that DHDK exerts its cardioprotective effect by activating the PPARG-CPT1B-FAO axis, effectively correcting lipid metabolic disorders. Given that lipid dysregulation is a hallmark of various internal metabolic diseases, DHDK may also hold therapeutic potential for other heart conditions driven by metabolic disturbances, such as diabetic cardiomyopathy, highlighting its broad relevance to the field of internal diseases.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Chemical Engineering Journal Advances
·
2023
·
IF 0
Yun-Da Yue,Yuan-Yuan Cui,Cheng-Xiong Yang
Rational design and fabrication of effective drug delivery systems (DDS) are crucial for improving the therapeutic effectiveness and overcoming the shortcomings of chemotherapy. Herein, we report the construction of a novel cyclodextrin microporous organic network (CD-MON)-based DDS via a convenient thiol‑yne click reaction and dehydration condensation modification for the controllable release and targeted delivery of doxorubicin (DOX), a typical chemotherapy drug. The constructed DDS afforded multiple hydrophobic, hydrogen-bonding, and host-guest interaction sites, allowing for the efficient loading of DOX. The obtained DDS also exhibited good sustained and long-term release of DOX. Additionally, the proposed DDS offers good biocompatibility and exhibits an obvious aggregation-induced emission. Furthermore, the introduction of folic acid (FA) into the CD-MON-based DDS provided excellent targeting capacity for FA receptor-positive NCI-H226 cells. This study proved the universality of the design, synthesis, and application of CD-MON-based DDS, revealing the great potential of CD-MONs in drug delivery.
✓ 已验证
DOI
CARBOHYDRATE POLYMERS
·
2024
·
IF 10.7
Junmin Qian,Abdalrheem Jarelnaby Musa Aldai,Weijun Xu,Taibing Wang,Kunkun Zhao,Yaping Wang,Jingjing Fan,Aili Suo
Cuproptosis shows great prospects in cancer treatments. However, insufficient intracellular copper amount, low-level redox homeostasis, and hypoxic tumor microenvironment severely restrict cuproptosis efficacy. Herein, hydrazided hyaluronan-templated decorated CuO 2 -doxorubicin (CuDT) nanodot clusters (NCs) are developed for efficient doxorubicin (DOX)-sensitized cuproptosis therapy in breast cancer via a three-pronged strategy. The CuDT NCs with an average size of 56.2 nm are fabricated from 3,3′-dithiobis(propionohydrazide)-conjugated hyaluronan, Cu 2+ , and DOX through a one-pot mineralization process. The CuDT nanoparticles exhibit pH-responsive H 2 O 2 , Cu 2+ , and DOX release profiles and catalytic activity. Upon entrance into tumor cells, CuO 2 -based exogenous H 2 O 2 supply and DOX-augmented endogenous H 2 O 2 generation jointly elevate intracellular H 2 O 2 level, which can further be transformed into hydroxyl radicals and O 2 through Fenton-like reaction to achieve oxidative stress amplification and hypoxia relief, respectively. Moreover, the CuDT NCs can efficiently deplete intracellular overexpressed glutathione via Cu 2+ /Cu + cycle and abundant disulfide bonds, further enhancing cellular oxidative stress. These results demonstrate that the novel CuDT NCs achieve DOX-sensitized cuproptosis in breast cancer cells through elevating copper level, amplifying oxidative stress and alleviating hypoxia, and display prominent in vivo antitumor efficacy. Such a three-pronged strategy of targetedly boosting cuproptosis in cancer cells represents a novel approach for antitumor treatments.
✓ 已验证
DOI
PubMed
高影响因子
COLLOIDS AND SURFACES B-BIOINTERFACES
·
2015
·
IF 4.152
Baocheng Tian,Yuanyuan Ding,Jian Han,Jing Zhang,Yuzhen Han,Jingtian Han
A novel targeting drug delivery system containing poly(styrene-alt-maleic anhydride) 58 -b-polystyrene 130 (P(St-alt-MA) 58 -b-PSt 130 ) as a copolymer backbone, N -acetyl glucosamine (NAG) as a targeting moiety was designed and synthesized. The NAG grafted copolymer (NAG-P(St-alt-MA) 58 -b-PSt 130 ) was characterized by FTIR and 1 H NMR. The NAG-P(St-alt-MA) 58 -b-PSt 130 nanoparticles exhibited spherical shapes with an average diameter about 56.27 ± 0.43 nm, low critical micelle concentration of 0.028 mg/mL, negative zeta potential −41.46 ± 0.99 mV, high drug loading 25.83 ± 1.09% and encapsulation efficiency 69.69 ± 3.98%. In vitro cell cytotoxicity was conducted to confirm the safety of the NAG-P(St-alt-MA) 58 -b-PSt 130 nanoparticles. Confocal laser scanning microscopy (CLSM) and flow cytometry (FCM) results showed that the NAG targeting moiety enhanced the internalization and targeting ability of NAG-P(St-alt-MA) 58 -b-PSt 130 nanoparticles. Anticancer activity toward MCF-7 cells and HT29 cells showed that DOX-loaded NAG-P(St-alt-MA) 58 -b-PSt 130 nanoparticles exhibited a higher antitumor activity compared to DOX-loaded P(St-alt-MA) 58 -b-PSt 130 nanoparticles, which could attribute to NAG receptor-mediated endocytosis. These results suggest that the biocompatible and non-toxic NAG-P(St-alt-MA) 58 -b-PSt 130 nanoparticles may be used as an effective targeting drug delivery system for cancer therapy.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Cell Death & Disease
·
2021
·Vol. 12
·期 5
·1-17
·
IF 8.469
Wang Ruoqin,Sun Linqing,Xia Suhua,Wu Hongya,Ma Yanchao,Zhan Shenghua,Zhang Guangbo,Zhang Xueguang,Shi Tongguo,Chen Weichang
Emerging evidence suggests that cellular senescence induced by chemotherapy has been recognized as a new weapon for cancer therapy. This study aimed to research novel functions of B7-H3 in cellular senescence induced by a low dose of doxorubicin (DOX) in colorectal cancer (CRC). Here, our results demonstrated that B7-H3 knockdown promoted, while B7-H3 overexpression inhibited, DOX-induced cellular senescence. B7-H3 knockdown dramatically enhanced the growth arrest of CRC cells after low-dose DOX treatment, but B7-H3 overexpression had the opposite effect. By RNA-seq analysis and western blot, we showed that B7-H3 prevented cellular senescence and growth arrest through the AKT/TM4SF1/SIRT1 pathway. Blocking the AKT/TM4SF1/SIRT1 pathway dramatically reversed B7-H3-induced resistance to cellular senescence. More importantly, B7-H3 inhibited DOX-induced cellular senescence of CRC cells in vivo. Therefore, targeting B7-H3 or the B7-H3/AKT/TM4SF1/SIRT1 pathway might be a new strategy for promoting cellular senescence-like growth arrest during drug treatment in CRC.
✓ 已验证
DOI
PubMed
高影响因子
Journal of Materials Chemistry B
·
2012
·Vol. 1
·期 3
·284-292
·
IF 0
Pengfei Gou,Wenwen Liu,Weiwei Mao,Jianbin Tang,Youqing Shen,Meihua Sui
The clinical utility of doxorubicin (DOX) is restricted by its severe side effects. Continuous efforts are aimed at developing efficacious DOX-delivery systems that may overcome the drawbacks of existing ones. Herein, we report a self-assembling prodrug forming high drug loading nanoparticles for DOX delivery. A low molecular weight polyethylene glycol (PEG) chain as the hydrophilic part was anchored to hydrophobic DOX via an acid-cleavable hydrazone bond to form the amphiphilic prodrug PEG–DOX. In aqueous solution, PEG–DOX formed nanoparticles with a diameter of ∼125 nm and extremely high drug loading (∼46 wt%). These nanoparticles were stable in PBS but released DOX in an acidic pH-triggered manner. Interestingly, taken up by cells via endocytosis, PEG–DOX bypassed the P-glycoprotein (P-gp)-mediated efflux of DOX, leading to drug accumulation in DOX-resistant human breast cancer cells (MCF-7/ADR). More importantly, PEG–DOX exhibited potent antitumor activity in vitro and in vivo, and showed significantly increased in vivo safety than free DOX. These encouraging data merit further preclinical and clinical development on PEG–DOX.
✓ 已验证
DOI
PubMed
Journal of Biomedical Nanotechnology
·
2016
·Vol. 12
·期 11
·1975-1986
·
IF 3.929
Zhang Min,Jiang Li
Mesoporous silica nanoparticles (MSNs) are widely used nanoparticles with a pore rich structure that is suitable for drug delivery. Here, we used MSNs to carry and deliver doxorubicin hydrochloride (DOX) in vivo to study the features of DOXloaded MSNs (MSNs@DOX). We used TEM
and zeta potential to illustrate that MSNs@DOX increase apoptosis and decrease metastasis of tumor cells. We used MTT, flow cytometry, Western blotting, wound healing, and transwell assays, as well as an in vivo metastasis model to explore the anti-carcinoma efficacy of MSNs@DOX. Our
results showed that DOX was efficiently loaded into MSNs measuring approximately 88±11 nm, which significantly increased the antitumor efficacy of DOX on lung cancer, both in vitro and in vivo, compared to a regular DOX treatment. MSNs@DOX markedly induced apoptosis through
cytochrome C release and the caspase family. Furthermore, cell migration and invasion were sharply inhibited, both in vitro and in vivo. We also found that the enhanced effect of MSNs@DOX might be due to an increased cellular uptake by tumor cells based on the enhanced permeability
and retention time of the nanoparticles. Matrigel plug assays and Western blotting assays revealed that the molecular mechanism behind the anti-metastasis effect might be attributed to the suppression of VEGF-mediated angiogenesis. Our results offer a new perspective on the application of
nanoparticles against metastasis.
✓ 已验证
DOI
PubMed
高影响因子
Current Drug Delivery
·
2024
·Vol. 22
·期 10
·1414-1429
·
IF 2.8
Houlin Su,Zhiqiang Tu,Lin Jing,Yanling Huang,Xu Liu,Mingqing Yuan
BackgroundCombining Doxorubicin (DOX) with sorafenib (SF) is a promising strategy for treating Hepatocellular Carcinoma (HCC). However, strict dosage control is required for both drugs, and there is a lack of target selectivity.ObjectiveThis study aims to develop a novel nano-drug delivery system for the combined use of DOX and SF, aiming to reduce their respective dosages, enhance therapeutic efficacy, and improve target selectivity.MethodsDOX/SF co-loaded liposomes (LPs) were prepared using the thin-film hydration method. The liposomes were modified with 1,2-distearoyl-sn-glycero-3-phospho-ethanolamine (DSPE)-polyethylene glycol (PEG2000), DSPE-PEG1000-cell penetrating peptide TAT, and Glycyrrhetinic Acid (GA). The basic properties of the liposomes were characterized. CCK-8 cell viability assays were conducted using HepG2, MHCC97-H, and PLC cell models, and apoptosis experiments were performed using HepG2 cells to determine if this delivery system could reduce the respective dosages of DOX and SF and enhance HCC cytotoxicity. Liposome uptake experiments were performed using HepG2 cells to validate the target selectivity of this delivery system.ResultsA GA/TAT-DOX/SF-LP liposomal nano drug delivery system was successfully constructed, with a particle size of 150 nm, a zeta potential of -7.9 mV, a DOX encapsulation efficiency of 92%, and an SF encapsulation efficiency of 88.7%. Cellular experiments demonstrated that this delivery system reduced the required dosages of DOX and SF, exhibited stronger cytotoxicity against liver cancer cells, and showed better target selectivity.ConclusionA simple and referenceable liposomal nano drug delivery system has been developed for the combined application of DOX and SF in hepatocellular carcinoma treatment.
✓ 已验证
DOI
高影响因子
COLLOIDS AND SURFACES A-PHYSICOCHEMICAL AND ENGINEERING ASPECTS
·
2026
·
IF 5.4
Xin Dang,Haiping Zhou,Hui Qi,Ruoru Qian,Jieru Xu
Insufficient therapeutic response in cervical cancer is closely associated with enhanced redox buffering, mitochondrial metabolic adaptation, and drug damage repair, which collectively weaken the sustained cytotoxicity of conventional chemotherapy. Herein, we developed a poly(2-ethyl-2-oxazoline) (PEOz)-modified Cu 2+ /Ca 2+ -coordinated doxorubicin (DOX)-loaded nanoplatform, D/CCP-P, to integrate chemotherapy, oxidative stress remodeling, cuproptosis sensitization, and photothermal amplification. In this system, Cu/Ca-doped mesoporous polydopamine served as both a drug-loading scaffold and photothermal converter, while PEOz enabled weakly acidic charge-reversal to enhance tumor cell uptake. The Cu/Ca dual-ion design was designed to disrupt intracellular redox and mitochondrial homeostasis: Cu 2+ was associated with glutathione depletion and reactive oxygen species accumulation, whereas Ca 2+ was associated with mitochondrial perturbation and metabolic stress, thereby weakening cellular tolerance to therapeutic insults. D/CCP-P exhibited efficient DOX loading, with a drug loading content of 42.64%. The nanoplatform also showed favorable photothermal performance, with a photothermal conversion efficiency of 41.43%, and enabled stimuli-responsive DOX release under acidic, reductive, and near-infrared (NIR) irradiation conditions. Mechanistically, D/CCP-P increased ROS-associated stress and altered NDUFS8/HSP70 expression, while time-course and Cu-MPDA/CCP comparisons supported progressive, Cu/Ca-amplified cuproptosis-related changes; HUVECs retained relatively high viability under non-irradiated conditions. Overall, this cascade nanotherapeutic strategy may enhance DOX-mediated cervical cancer therapy through redox remodeling–cuproptosis sensitization–photothermal amplification. Download: Download high-res image (237KB) Download: Download full-size image
✓ 已验证
DOI
高影响因子
TALANTA
·
2026
·
IF 6.7
Ruyu Li,Tingting Zhang,Lijie Zhou,Jingjing Feng,Longgang Wang,Haiyan Xiao
Pd 3 Au-LCLP NPs-DOX with anti-protein adsorption properties was prepared. • Pd 3 Au-LCLP NPs-DOX exhibit good enzyme-like activity and photothermal performance. • More DOX was released under the irradiation of 808 nm laser. • Pd 3 Au-LCLP NPs-DOX shows significant anti-tumor effects by multi-therapy. Traditional cancer therapies are limited by severe side effects and therapeutic challenges, while noble metal nanozymes offer promising enzyme-like therapeutic potential but remain constrained by poor aqueous stability. In this work, palladium-gold bimetallic nanoparticles (Pd 3 Au-LCLP NPs) with peroxidase-like activity were constructed using Leonurus cardiaca L. polysaccharide as both a reducing agent and stabilizing template, and further loaded with doxorubicin (DOX) to form Pd 3 Au-LCLP NPs-DOX. The resulting nanoplatform exhibited excellent water dispersibility, structural stability, anti-protein adsorption capability, and enhanced photothermal conversion performance. Under 808 nm laser irradiation, Pd 3 Au-LCLP NPs-DOX achieved a cumulative DOX release of 81% at pH 5.5. In vitro , it showed significant cytotoxicity against A549 and HeLa cells. In vivo , the tumor inhibition rate reached 82.6%. Overall, this combined therapeutic strategy integrating chemodynamic therapy (CDT), photothermal therapy (PTT), and chemotherapy (CT) demonstrated strong synergistic anti-tumor efficacy. Download: Download high-res image (393KB) Download: Download full-size image
✓ 已验证
DOI
高影响因子
危险品化学品经营许可证（带存储）