MICROCHIMICA ACTA
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2026
·Vol. 193
·期 9
·649
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IF 5.4
Cai Chuangui,Lin Zhen,Yao Wensong,Lian Shan,Huang Kaiyuan,Deng Haohua,Lin Xinhua,Chen Wei
Arginine surface-engineered 6-aza-2-thiothymine gold nanoclusters (Arg/ATT-AuNCs) via host-guest assembly were synthesized which exhibit exceptional catalytic activity and intense photoluminescence. Arg/ATT-AuNCs enhanced the CL intensity from NaIO 4 -H 2 O 2 system by 1200-fold. The CL mechanistic studies revealed that Arg/ATT-AuNCs not only accelerated decay of H 2 O 2 to form reactive oxygen species, but also acted as efficient energy acceptors of singlet oxygen ( 1 O 2 ) via a CL resonance energy transfer (CRET) pathway. It was observed that doxorubicin (DOX) quenches the CL signal through an inner filter effect that disrupts the CRET process. Based on this, a straightforward, rapid, and highly sensitive biosensor has been developed for the detection of DOX in human serum samples, achieving a low detection limit of 0.029 µM. The biosensor was applied to DOX determination in human serum samples with recoveries ranging from 91.1 to 106.2%. This study not only provides a new method for the detection of DOX, but also broadens the application scope of AuNCs in the field of CL. Graphical
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JOURNAL OF FLUORESCENCE
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2023
·
IF 2.7
Mo Jingwen,Wang Shichang,Zeng Jiaying,Ding Xiong
Doxorubicin is a common chemotherapeutic drug used to treat a variety of cancers. Monitoring the concentration of doxorubicin in human biological fluids is vital for treatment. In this work, we report an aptamer-functionalized, 808 nm-excited core–shell upconversion fluorescence sensor for specific detection of doxorubicin (DOX). Upconversion nanoparticles and DOX are used as energy donors and energy acceptors respectively. Aptamers immobilized on the surface of upconversion nanoparticles act as the molecular recognition element for DOX. The binding of DOX to the immobilized aptamers results in the fluorescence quenching of the upconversion nanoparticles via a fluorescence resonance energy transfer process. The relative fluorescence intensity exhibits a good linear response to DOX concentration in the range of 0.5 μM to 55 μM with a detection limit of 0.5 μM. The aptasensor displays high specificity and anti-interference against other antibiotics, common ions, and biomolecules owing to strong and specific interactions of aptamers towards DOX. The sensor is further applied for the detection of DOX in urine with spike recoveries of nearly 100%.
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COLLOIDS AND SURFACES B-BIOINTERFACES
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2019
·
IF 3.973
Si Sun,Nihad Cheraga,Han-Ning Jiang,Qian-Ru Xiao,Peng-Cheng Gao,Yang Wang,Ying-Ying Wei,Xiao-Wei Wang,Yong Jiang
A variety of three-dimensional DNA assemblies have been proposed as drug carriers owing to their good biocompatibility and easy fabrication. In this study, inspired by the structure of cockleburs, a novel aptamer-tethered DNA assembly was developed for effective targeted drug delivery. The Apt-nanocockleburs were fabricated via a facile process of DNA base pairing: four complementary DNA single strands, including one aptamer-ended strand and three sticky-end strands, were applied to pair with each other. The main body of the nanocockleburs can load doxorubicin (Dox) whilst the covered aptamer spines bind to the target MCF-7 cells. The self-assembled Apt-nanocockleburs exhibit higher cell uptake as well as increased cytotoxicity to MCF-7 cells than DNA nanocockleburs without aptamers. This study provided a DNA constructing platform to produce new drug carriers with high selectivity for cancer targeted drug delivery.
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Materials Science & Engineering C-Materials for Biological Applications
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2015
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IF 3.088
Minghui Xu,Junmin Qian,Xuefeng Liu,Ting Liu,Hongjie Wang
In recent years, stimuli-sensitive prodrugs have been extensively studied for the rapid “burst” release of antitumor drugs to enhance chemotherapeutic efficiency. In this study, a novel stimuli-sensitive prodrug containing galactosamine as a targeting moiety, poly(ethylene glycol)–doxorubicin (PEG–DOX) conjugate, was developed for targeting HepG2 human liver cancer cells. To obtain the PEG–DOX conjugate, both galactosamine-decorated poly(ethylene glycol) aldehyde (Gal-PEG-CHO) and methoxy poly(ethylene glycol) aldehyde (mPEG-CHO) were firstly synthesized and functionalized with dithiodipropionate dihydrazide (TPH) through direct reductive amination via Schiff's base formation, and then DOX molecules were chemically conjugated to the hydrazide end groups of TPH-functionalized Gal-/m-PEG chains via pH-sensitive hydrazone linkages. The chemical structures of TPH-functionalized PEG and PEG–DOX prodrug were confirmed by 1 H NMR analysis. The PEG–DOX conjugate could self-assemble into spherical nanomicelles with a mean diameter of 140 nm, as indicated by transmission electron microscopy and dynamic light scattering. The drug loading content and loading efficiency in the prodrug nanomicelles were as high as 20 wt.% and 75 wt.%, respectively. In vitro drug release studies showed that DOX was released rapidly from the prodrug nanomicelles at the intracellular levels of pH and reducing agent. Cellular uptake and MTT experiments demonstrated that the galactosamine-decorated prodrug nanomicelles were more efficiently internalized into HepG2 cells via a receptor-mediated endocytosis process and exhibited a higher toxicity, compared with pristine prodrug nanomicelles. These results suggest that the novel Gal-PEG–DOX prodrug nanomicelles have tremendous potential for targeted liver cancer therapy.
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JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS
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2020
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IF 3.209
Yuhuan Ji,Xueyuan Zhang,Jinzhi Liu,Yu Chen,Min Meng,ChunLei Li,Laixin Wang
Regulatory guidance requires the quantification of encapsulated and free doxorubicin for a liposomal doxorubicin injection bioequivalence study. Due to the instability of liposome formulations in plasma samples, the release of free drug from the liposomal encapsulated doxorubicin during sample handling would result in elevation of measured free doxorubicin concentration. To prevent the potential release of free drug, stabilizer reagents and procedures were successfully developed and validated to adequately stabilize liposomal drugs in plasma samples during sample collection, storage and extraction. Three LC–MS/MS methods were developed and fully validated for direct quantitation of free, encapsulated and total doxorubicin concentrations in human plasma according to relevant regulatory guidance: Method 1: Quantitation of free doxorubicin and doxorubicinol at a linear range of 1−400 ng/mL and 0.5−10 ng/mL, respectively, from stabilizer treated plasma samples using solid phase extraction (SPE); Method 2: Quantitation of encapsulated doxorubicin at a linear range of 50−50,000 ng/mL from the stabilizer treated plasma sample using SPE followed by PPE extraction method; Method 3: Quantitation of total concentration of doxorubicin from untreated plasma samples at a linear range of 50−50,000 ng/mL using PPE. All three methods were successfully used to support a bioequivalence study between Caelyx® and Duomeisu® (Doxorubicin Hydrochloride Liposomal injection, generic doxorubicin formulation produced by CSPC). Incurred sample reanalysis (ISR) passing rate for total doxorubicin, free doxorubicin/doxorubicinol, and encapsulated doxorubicin methods were 100 %, 84.7 %/100 %, and 98.5 %, respectively. The measured total doxorubicin concentrations matched the sum of free and encapsulated doxorubicin concentrations.
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Materials Science & Engineering C-Materials for Biological Applications
·
2014
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IF 2.736
Jian-Tao Lin,Ying Zou,Chao Wang,Yue-Chun Zhong,Yi Zhao,Hui-Er Zhu,Guan-Hai Wang,Li-Ming Zhang,Xue-Bao Zheng
Cationic micellar nanoparticles for chemotherapeutic drugs and therapeutic gene co-delivery were prepared based on a poly-( N -ε-carbobenzyloxy- l -lysine) (PZLL) and dendritic polyamidoamine (PAMAM) block copolymer (PZLL-D3). PZLL-D3 was synthesized by a copper-catalyzed azide alkyne cyclization (click) reaction between α-alkyne-PZLL and azide focal point PAMAM dendrons. Its structure was characterized by 1 H NMR and FTIR, and its buffering capability was determined by acid–base titration. MTT, agarose gel electrophoresis and flow cytometry studies showed that PZLL-D3 revealed low in vitro cytotoxicity, strong pDNA condensation ability, protection of pDNA against deoxyribonuclease I degradation and high gene transfection efficiency in 293T and HeLa cells. In addition, the micellar nanoparticles delivered pDNA and anticancer drug doxorubicin (DOX) simultaneously and efficiently to tumor cells, and the DOX loaded nanoparticles showed sustained in vitro release at pH = 7.4 and 5.8.
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Oxidative Medicine and Cellular Longevity
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2014
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IF 3.363
Siying Li,Wenjuan Wang,Ting Niu,Hui Wang,Bin Li,Lei Shao,Yimu Lai,Huanjie Li,Joseph S. Janicki,Xing Li Wang,Dongqi Tang,Taixing Cui
The anticancer therapy of doxorubicin (Dox) has been limited by its acute and chronic cardiotoxicity. In addition to a causative role of oxidative stress, autophagy appears to play an important role in the regulation of Dox-induced cardiotoxicity. However, the underlying mechanisms remain unclear. Accordingly, we explored a role of nuclear factor erythroid-2 related factor 2 (Nrf2) in Dox-induced cardiomyopathy with a focus on myocardial oxidative stress and autophagic activity. In wild type (WT) mice, a single intraperitoneal injection of 25 mg/kg Dox rapidly induced cardiomyocyte necrosis and cardiac dysfunction, which were associated with oxidative stress, impaired autophagy, and accumulated polyubiquitinated protein aggregates. However, these Dox-induced adverse effects were exaggerated in Nrf2 knockout (Nrf2−/−) mice. In cultured cardiomyocytes, overexpression of Nrf2 increased the steady levels of LC3-II, ameliorated Dox-induced impairment of autophagic flux and accumulation of ubiquitinated protein aggregates, and suppressed Dox-induced cytotoxicity, whereas knockdown of Nrf2 exerted opposite effects. Moreover, the exaggerated adverse effects in Dox-intoxicated Nrf2 depleted cardiomyocytes were dramatically attenuated by forced activation of autophagy via overexpression of autophagy related gene 5 (Atg5). Thus, these results suggest that Nrf2 is likely an endogenous suppressor of Dox-induced cardiotoxicity by controlling both oxidative stress and autophagy in the heart.
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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.
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Journal of Cancer
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2019
·
IF 3.182
Yong-lin Lu,Ya-bin Ma,Chan Feng,Dong-lei Zhu,Jie Liu,Lv Chen,Shu-jing Liang,Chun-yan Dong
Combination chemotherapy is considered to be one of the most effective treatments for breast cancer by reducing the emergence of drug resistance. In this study, a novel drug delivery system based on bovine serum albumin nanoparticles (BSA NPs) was successfully developed. Doxorubicin (DOX) and cyclopamine (CYC), a potential anti-cancer agent that inhibits the hedgehog signaling pathway were entrapped into BSA NPs through electrostatic interactions and hydrophobic interactions, respectively. Rather than simple combination of two different chemotherapeutics, the CYC also increased the intracellular DOX accumulation by decreasing the expression of P-glycoprotein (P-gp), which could thus reverse the DOX resistance. Tumor-targeting property of nanoparticles was the prerequisite for its further application. Interestingly, retention of fluorescently-labeled particles in vivo indicated that the dual-drug-loaded BSA NPs could not only target the primary tumors, but also target the metastatic lymph nodes, which would simultaneously inhibit the tumor growth and distant metastasis. Taken together, this study provides a promising strategy for co-delivery of drugs, tumor and metastatic lymph node targeting, and DOX resistance reversing in breast cancer chemotherapy.
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INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2026
·
IF 8.7
Shuiling Qin,Wei Zhang,Yanjie Luo,Xin Tang,Wei Wu
Oral administration remains the most convenient and patient-preferred route for therapeutic drug delivery. However, the clinical translation of oral doxorubicin (DOX) is severely hampered by its low oral bioavailability, which remains a major challenge for oral chemotherapy. Herein, we report the development of taurine-conjugated chitosan (TAU-CS)-modified liposomes co-encapsulating silybin (SLB) and DOX (designated TAU-CS/LIP@DOX + SLB), a system engineered to enhance the oral bioavailability of DOX while reducing DOX-induced cardiomyocyte toxicity in vitro . The optimized liposomes displayed a homogeneous spherical morphology, with a mean particle size of 183.7 nm, a zeta potential of +9.89 mV, and encapsulation efficiencies over 90% for both active pharmaceutical ingredients. TAU-CS functionalization significantly augmented the mucoadhesion of the liposomes, resulting in 2.08-fold higher cellular uptake in Caco-2 cells relative to free DOX. In vitro cytotoxicity assessments demonstrated that TAU-CS/LIP@DOX + SLB reduced DOX-induced toxicity in H9C2 cardiomyocytes compared with free DOX and the other tested formulations. Remarkably, TAU-CS/LIP@DOX + SLB achieved an absolute oral bioavailability of 28.89% and a 73.38% inhibition rate against CYP3A4. Collectively, these findings establish taurine transporter (TAUT)-targeted DOX/SLB co-loaded liposomes as an oral delivery platform that enhances DOX systemic exposure through intestinal uptake and metabolic-barrier modulation while reducing DOX-induced cardiomyocyte toxicity in vitro . TAU-CS-functionalized liposomes integrate gastrointestinal protection, mucoadhesion, TAUT-associated epithelial uptake, and SLB-mediated metabolic-barrier modulation to enhance oral DOX absorption. This multifunctional co-delivery strategy simultaneously improves DOX systemic exposure and reduces DOX-induced cardiomyocyte toxicity in vitro . Download: Download high-res image (127KB) Download: Download full-size image
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ACS Nano
·
2025
·
IF 16
Tianshu Hao,Hanze Guo,Chenyuan Wang,Shisuo Jing,Wen Zhang,Yongnian Zeng,Jinxuan Hou,Zhiyin Song,Wei Li
Mitochondrial hyperfunction in doxorubicin (DOX)-resistant breast cancer cells mitigates oxidative stress, contributing to chemoresistance. Here, we present a precise mitochondria-targeted microneedle (MN) delivery strategy incorporating hollow DOX-TPP@ZIF-67 nanoparticles to overcome chemotherapy resistance. This platform was synthesized by loading mitochondria-targeted DOX-TPP into ZIF-67 structures and embedded into fast-dissolving MN patches for localized, organelle-specific drug delivery. Mitochondrial accumulation of DOX-TPP induces ROS overproduction, triggering apoptosis, disrupting cystine–cysteine conversion, depleting glutathione (GSH), and inactivating GPX4. The resulting oxidative imbalance promotes lipid peroxidation and ferroptosis. Additionally, the hydrogen peroxide generated during metabolic reprogramming drives further ferroptosis via the Fenton-like reaction. This approach effectively suppresses the growth of chemoresistant tumors and prolongs survival in DOX-resistant animal models. Our results demonstrate that mitochondria-targeted MN delivery provides a precise strategy to overcome chemoresistance and uncover a mechanism by which enhanced anthracycline efficacy drives the synergistic activation of mitochondrial dysfunction, apoptosis, and ferroptosis.
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Molecular Medicine Reports
·
2025
·Vol. 32
·期 3
·1-12
·
IF 3.5
Kaixiang Zhao,Shaochen Wang,Dandan Feng,Dongwei Wang,Guang Yang,Fangfang Lang
The specific mechanisms of doxorubicin (Dox)‑induced cardiotoxicity (DIC) remain unclear. In the present study, H9c2 cardiomyocytes were treated with Dox, and it was revealed that DEAD‑box RNA helicase 3 X‑linked (DDX3X), mitochondrial antiviral signaling (MAVS) and stress granules (SGs) were present at lower levels in the treated H9c2 cardiomyocytes compared with those in the control cells. The present study further investigated the mechanisms through which DIC occurs. Pretreatment with arsenite, which pharmacologically accelerates SGs, alleviated the myocardial injury caused by Dox. By contrast, anisomycin, an SG inhibitor, increased cardiomyocyte apoptosis induced by Dox. In addition, both DDX3X knockdown and pretreatment with RK‑33 (a DDX3X pharmacological inhibitor) decreased SG expression, whereas DDX3X overexpression promoted SG generation. These results indicated that DDX3X mitigated DIC through the regulation of SGs. In addition, MAVS knockdown inhibited SG assembly and reduced the expression of the anti‑apoptotic inhibitor Bcl2, and MAVS was influenced by DDX3X, thereby serving as a connector between DDX3X and SGs. The results from western blotting, reverse transcription‑quantitative PCR, immunofluorescence and flow cytometry analysis demonstrated that DDX3X, MAVS, and SGs may serve as key protective factors in DIC.
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