JOURNAL OF DRUG DELIVERY SCIENCE AND TECHNOLOGY
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2024
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IF 4.5
Jingmou Yu,Qinglan Yuan,Chuan Li,Sile Hong,Yuting Li,Yafen Li,Jing Ren,Dengzhao Jiang,Pu Chen,Lei Zhang
The efficient drug release triggered by the tumor microenvironment is challenging in the development of stimuli-sensitive nanomedicine. In this study, we developed novel polymeric micelles sensitive to reactive oxygen species (ROS) for targeted delivery of doxorubicin (DOX) in tumor therapy. Hydrophilic chondroitin sulfate A (CSA) was conjugated with cholesteryl hemisuccinate (CHS) via a ROS-cleavable thioketal (TK) bond. The resulting CSA-TK-CHS could form self-assembled micelles, and DOX-loaded CSA-TK-CHS (CSA-TK-CHS/DOX) micelles displayed a nearly spherical shape with an average hydrodynamic diameter of 324 nm. The bioresponsive DOX release of CSA-TK-CHS/DOX micelles was evaluated in an H 2 O 2 -containing phosphate buffer solution (PBS). CSA-TK-CHS/DOX micelles showed higher cellular uptake than free DOX in 4T1 cells by confocal laser scanning microscopy (CLSM) observation. And CSA-TK-CHS/DOX improved DOX cytotoxicity against CD44-overexpressed 4T1 and CT26 tumor cells. Notably, CSA-TK-CHS/DOX micelles displayed significantly stronger potency ( P < 0.01) in antitumor activity than DOX·HCl in orthotropic 4T1-bearing Balb/c mice. Overall, these findings indicate that amphiphilic CSA-TK-CHS micelles are a promising targeted and intelligent drug carrier for tumor therapy.
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Frontiers in Pharmacology
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2026
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IF 5.4
Jing Ren,Yibo Yang,Guangdong Li,Huiying Sha,Bing Wang,Yin Wang,Ning Cui,Taoyan Liu
Introduction Doxorubicin (DOX)-induced cardiotoxicity (DIC) is a major clinical challenge, with early metabolic reprogramming acting as a potential pathogenic driver. This study investigates the early lipid metabolic disturbances in DIC and evaluates the cardioprotective potential of the natural metabolic modulator, chlorogenic acid (CGA). Methods Transcriptomic analysis was utilized to identify initial metabolic alterations. Lipidomics and spatial metabolomics were performed to map lipid distributions in DOX-treated H9c2 cardiomyocytes and C57BL/6J mouse hearts. The therapeutic mechanisms of CGA were assessed in vivo through echocardiography and histopathology, and in vitro using pharmacological interventions targeting the PPAR-FAO axis. Results Transcriptomics and lipidomics revealed that DOX significantly suppresses the PPAR signaling pathway and fatty acid oxidation (FAO), resulting in the accumulation of ceramides and long-chain acylcarnitines. Spatial metabolomics confirmed in situ myocardial acylcarnitine accumulation. CGA treatment effectively improved cardiac function, mitigated oxidative stress, and inhibited apoptosis. Mechanistically, CGA reduced mitochondrial ROS and acylcarnitine levels by restoring PPAR expression and promoting FAO. Pharmacological blockade of PPARα or exogenous addition of acylcarnitines completely abolished CGA’s protective effects. Discussion Impaired FAO and the subsequent accumulation of toxic acylcarnitines serve as early drivers of DOX-induced metabolic dysfunction. Targeting this lipid metabolic dysregulation with CGA represents a promising therapeutic strategy for mitigating anthracycline-induced cardiotoxicity.
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MOLECULAR PHARMACEUTICS
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2026
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IF 4.9
Fangzhou Yang,Yunqian Lu,Xiaoxue Lang,Lina Sun,Hang Zou,Ziting Zhou,Yaoyao Guo,Yifei Guo,Xiangtao Wang,Meihua Han
Whole cells serve as promising carriers for delivering bioactive molecules owing to their superior biocompatibility, minimal immunogenicity, and extended circulation time. In addition to preserving the intact cellular structure and functions, they provide abundant tumor-associated antigens as immune targets, providing a basis for tumor vaccine development. However, conventional chemotherapy with doxorubicin (DOX) suffers from limited tumor-targeting ability and severe systemic toxicity, which markedly restrict its therapeutic efficacy. In this study, we establish a simple liquid nitrogen freezing strategy to load DOX into liquid-nitrogen-treated (LNT) tumor cells for homologous targeting of breast cancer. The optimized formulation achieved a DOX loading of 38.28 ± 1.61 μg/5 × 106 cells. Both in vitro and in vivo studies confirm that the prepared DOX/LNT cell formulation exhibits excellent safety with no proliferative or pathogenic potential. Regarding the antitumor effect of DOX/LNT cells, in vitro cytotoxicity assays reveal an IC50 value of 1.104 μg/mL, representing a 1.87-fold improvement over free DOX. Furthermore, DOX/LNT cell achieves superior antitumor efficacy by combining chemotherapy with the activation of antitumor immune responses. Following intravenous administration via tail vein injection, in vivo studies demonstrated a tumor inhibition rate of 81.81%, extending the average survival time of breast tumor-bearing mice to 56 days. This approach offers a novel drug delivery system with improved tumor-targeting specificity, representing a precise and effective therapeutic strategy that integrates chemotherapy and immunotherapy for breast cancer treatment.
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Cardiovascular Therapeutics
·
2026
·Vol. 2026
·期 1
·8444915
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IF 2.8
Weijun Li,Zhenyu Zhao,Xuefeng Lin,Guoliang Chen,Lin Li,Ge Fang,Zhixi Hu
Objective This study is aimed at evaluating the effects of Zhenwu Decoction (ZWD) on cardiac dysfunction, water-retention–related phenotypes, and brain and kidney injury in rats with doxorubicin-induced chronic heart failure (CHF), and at examining whether these effects were accompanied by changes in AVP, V2R, PKA-C α , and AQP2-related markers. Methods Rats that met the prespecified CHF criteria after doxorubicin administration were rerandomized to the model, ZWD-L, ZWD-M, ZWD-H, or tolvaptan groups and treated once daily for 14 consecutive days. Cardiac function, biochemical and water balance–related outcomes, histopathology, brain AVP, and renal V2R, PKA-C α , and AQP2 expression were assessed. The animal was the experimental unit, and the number analyzed is reported for each outcome. Results Compared with the control group, model rats showed impaired cardiac function; increased ascites and tissue water retention; reduced 24-h urine output; histological injury in the heart, brain, and kidney; and altered AVP, V2R, PKA-C α , and AQP2-related markers. ZWD treatment was associated with improvement in these measured outcomes, with the magnitude and statistical support varying across doses. Tolvaptan produced the expected aquaretic reference response. Adjusted p values and the number of animals analyzed are reported for each outcome. Conclusion In this doxorubicin-induced CHF model, ZWD improved cardiac function and water-retention–related phenotypes and was accompanied by changes in AVP, V2R, PKA-C α , and AQP2-related markers. These data support an association but do not establish pathway mediation, direct target engagement, or heart–brain–kidney crosstalk.
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NAUNYN-SCHMIEDEBERGS ARCHIVES OF PHARMACOLOGY
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2026
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IF 4
Mu Shengmou,Liu Baolai
Doxorubicin (DOX), a natural compound with anticancer properties, is limited in its therapeutic application by low bioavailability and inadequate solubility. This paper presents a novel nanoparticle system designed to tackle these challenges by self-assembled DOX, polydopamine (PD) altered, and macrophage membrane (MM) coated nanoparticles (DOX-PD@MM NPs). The DOX-PD@MM NPs exhibited significant antitumor efficacy, elevated drug-loading capacity, enhanced stability, and exceptional photothermal properties. Further, the macrophage membrane endows the DOX-PD@MM NPs with active targeting to cancer tissues. We employed the U87-MG glioblastoma cell line to assess the in vitro anticancer activity of DOX-PD@MM. The findings indicate that DOX-PD@MM may efficiently induce cell death by producing reactive oxygen species (ROS) and releasing DOX. The amalgamation of DOX-PD@MM and near-infrared irradiation significantly enhanced anticancer efficacy by promoting DOX release and photothermal treatment. The DOX-PD@MM system enables drug delivery for poorly soluble drugs, thereby harnessing their full anticancer potential.
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JOURNAL OF MATERIALS SCIENCE
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2026
·Vol. 61
·期 25
·18185-18209
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IF 4.4
Li Ying,Qin Jiaying,Zhou Yiqing,Fang Baoru,Wang Ke,Wu Shang,Qian Huifeng,Xing Guiying,Li Xiudong,Ye Zhiqiu,Yu Zhangsen
Doxorubicin (DOX) is a highly effective first-line chemotherapeutic agent for various tumors. However, its clinical utility is limited by fatal dose-dependent cardiomyopathy, primarily attributed to excessive reactive oxygen species (ROS) production and mitochondrial damage. Herein, we developed ultrasmall Prussian blue nanoparticles (SPB) possessing multiple antioxidant enzyme-like activities for the prevention and treatment of doxorubicin-induced cardiomyopathy (DIC). These nanoparticles function by efficiently scavenging ROS and preserving mitochondrial integrity. In vitro studies in cardiomyocytes demonstrated that SPB effectively eliminated ROS, reversed mitochondrial membrane potential loss, enhanced mitochondrial complex I activity, promoted ATP production, attenuated mitochondrial dysfunction, and inhibited cardiomyocyte apoptosis. In a breast cancer-bearing mouse model, SPB administration protected cardiac function and reduced myocardial fibrosis without compromising the antitumor efficacy of DOX. Mechanistically, SPB upregulated antioxidant-related proteins to reduce oxidative stress by activating the Keap1-Nrf2/HO-1 signaling pathway. Acute toxicity experiments showed that SPB could be safely administered via the tail vein at a dose of 75 mg/kg, which is substantially above the effective therapeutic dose. In conclusion, these findings demonstrate that SPB confers robust cardioprotection during DOX chemotherapy and holds considerable promise for clinical translation. Graphical Ultrasmall Prussian blue nanoparticles (SPB), synthesized via a green chemistry method with excellent biocompatibility, can effectively protect the heart function of chemotherapy tumor-bearing mice by scavenging reactive oxygen species generation, activating the Keap1-Nrf2/HO-1 signal pathway and protecting mitochondrial functions, reducing the degree of myocardial fibrosis without weakening the chemotherapy efficacy of DOX.
The alternative text for this image may have been generated using AI.
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Journal of Materials Chemistry B
·
2025
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IF 5.7
Yishun Yang,Yue Ding,Tong Zhang
Icariside II (ICAII), a bioactive compound from Epimedii Folium, exhibits promising anti-tumor activity but faces challenges in clinical application due to poor solubility and low bioavailability. This study developed a novel carrier-free co-delivery system of ICAII and doxorubicin (DOX) through self-assembly into nanofibers. The ICAII combined with DOX nanofibers (ICAII-DOX NFs) and ICAII-DOX/TPGS NFs (with TPGS as a stabilizer) were systematically characterized for their physicochemical properties, including size distribution, morphology, and molecular interactions. The synergistic anti-lung cancer effect of ICAII and DOX was evaluated both in vitro and in vivo. The prepared ICAII-DOX NFs and ICAII-DOX/TPGS NFs showed mean sizes of 127 and 338 nm respectively, with PDI values of 0.2~0.3 and drug loading contents > 48%. FTIR, fluorescence, NMR and X-ray powder diffraction analyses revealed that the formation of ICAII-DOX co-assembly was primarily driven by intermolecular hydrogen bonding between the two molecules. The nanofibers demonstrated controlled drug release profiles (DOX’s cumulative release rate was 65.88% at 48 h, and ICAII’s cumulative release rate was 74.29% at 48 h) and enhanced cellular uptake (1.8-fold more than free DOX group). CCK-8 assay results showed that the IC50 (calculated in term of DOX) of ICAII-DOX mixture, ICAII-DOX NFs and ICAII-DOX/TPGS NFs were 0.67, 0.60 and 0.44 μM on A549 human lung carcinoma cells. In vivo studies using an A549 xenograft mouse model showed improved therapeutic efficacy (the inhibition rates of ICAII-DOX Mixture and ICAII-DOX/TPGS NFs groups were 29.90%) compared to single drug treatment (the inhibition rates of DOX and ICAII groups were 8.70% and 17.72%). This study presents a self-assembled carrier-free co-delivery system, providing a potential strategy for treating lung cancer.
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Biomaterials Advances
·
2025
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IF 6
Qiwei Li,Liming Zhang,Ze Liu,Yue Yang,Yijia Guan,Jianguo Liao,Yanru Zhang
Osteosarcoma, a malignant tumor, often results in significant bone defects following surgical resection, accompanied by challenges of recurrence and metastasis. In this study, a mesoporous bio-glass doped with Li + to promote angiogenesis and Zn 2+ to provide antibacterial properties (Li/Zn-MBG) was synthesized as a carrier for the anticancer drug doxorubicin hydrochloride (DOX). The drug-loaded Li/Zn-MBG (Li/Zn-MBG@DOX) was then incorporated into a chitosan (CS)/polyacrylamide (PAM) dual-network hydrogel to form the Li/Zn-MBG@DOX/CS/PAM hydrogel. Results showed that the inclusion of Li + and Zn 2+ enhanced the mesoporous structure and dispersibility of MBG, resulting in more uniform particles (178.4 ± 7.1 nm), higher specific surface area (102.93 m 2 ·g −1 ), pore volume (0.26 cm 3 ·g −1 ), and pore diameter (9.62 nm). Moreover, the drug loading and encapsulation efficiencies were increased to 23.95 % and 95.80 %, respectively, with sustained DOX release over 14 days (24.30 ± 0.17 %). The Li/Zn-MBG@DOX/CS/PAM hydrogel exhibited a stable three-dimensional porous structure with uniform internal pores and demonstrated favorable mechanical properties, including a compressive strength of 762.00 ± 0.55 kPa and a swelling rate of 800–900 %. Cell experiments revealed that the composite hydrogel promoted the proliferation and differentiation of mouse bone marrow stromal stem cells (BMSCs) while inhibiting the proliferation and differentiation of human osteosarcoma cells (U2OS). In vivo studies showed that in mice with femoral defects treated with the Li/Zn-MBG@DOX/CS/PAM hydrogel, nearly all defects healed by week 12 with minimal inflammation. These findings suggest that the Li/Zn-MBG@DOX/CS/PAM composite hydrogel holds significant promise for the repair of bone defects following osteosarcoma surgery.
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Applied Materials Today
·
2026
·
IF 6.9
Zimo Zhang,Yeyang Wu,Mingyu Xing,Mingshuang Zhang,Saima Sadaf,Ya Wang
Localized neoadjuvant chemotherapy (NACT) is a widely utilized strategy for breast cancer treatment, aimed at reducing tumor size before surgery and improving rates of pathological complete response (pCR), a critical indicator of favorable long-term outcomes. However, the therapeutic efficacy of NACT is often limited by conventional drug delivery systems, which fail to achieve sufficient drug concentrations within the crucial early treatment window due to slow and nonspecific drug release. To address this challenge, we have fabricated an injectable, pH and thermal dual sensitive microgel by the copolymerization of N-isopropylacrylamide (NIPAM), N-isopropylmethacrylamide (NIPMAM), and methacrylic acid (MAA). These microgels are specifically designed to respond to the acidic and hyperthermic conditions of the breast tumor microenvironment (TME), enabling a tumor-specific burst release of encapsulated drug doxorubicin (DOX). Under simulated TME conditions (pH 5.0, 42°C), the microgels achieve a significant initial burst release of 58.99 % DOX within 4 h, compared to only 21.00 % under physiological conditions (pH 7.4, 37°C). In vitro studies further demonstrate that DOX-loaded microgels could reduce the viability of MCF-7 breast cancer cells to 39.36 % after 48 h at a DOX-equivalent concentration of 4.0 µg/mL. Furthermore, the microgels could effectively mitigate the cytotoxic effects of high concentration DOX on normal cells, preserving greater cell viability compared to free DOX. These findings highlight the potential of this dualsensitive microgel system as an innovative platform for localized NACT, offering enhanced therapeutic efficacy, improved pCR rates, and reduced systemic toxicity.
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JOURNAL OF NANOBIOTECHNOLOGY
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2026
·
IF 12.6
Jingya Xiu,Lin Liu,Lingao Yin,Yihong Peng,Ziqi Li,Ziyun Lin,Yilin Song,Degong Yang,Jiulong Zhang,Chunrong Yang
Immunogenic cell death (ICD), instigated by reactive oxygen species (ROS), has emerged as an efficacious strategy for augmenting the immunogenicity of tumor cells. However, the effects of ICD are severely diminished by elevated levels of glutathione (GSH) within tumor cells to maintaining intracellular redox homeostasis. To address this, the novel carrier-free self-assembled nanoparticles are designed to aggravating redox dyshomeostasis by reducing GSH and increasing ROS levels. The nanoparticles (ZDS NPs) were established by the self-assembly of zinc ions (Zn 2+ ), doxorubicin (DOX) and Nrf2 siRNA. The ZDS NPs exhibited the ultra-high entrapment efficiency of DOX (99%) and siRNA (89%), and the releases of DOX and siRNA were both pH-dependent owing to the cleavage of coordinate and hydrogen bonds under acidic conditions. Following the endocytosis of ZDS NPs by tumor cells, redox homeostasis was significantly disrupted, DOX and Zn 2+ enhanced the production of ROS via activating cGAS/STING pathway, whereas siRNA reduced GSH levels by decreasing the expression of Nrf2 protein. This further promoted a stronger ICD effect with elevated secretion of ATP, HMGB1, CRT, thereby inducing the maturation of DCs and activating a more robust anti-tumor immunity. This study presents a novel approach for the synergistic enhancement of ICD in cancer immunotherapy.
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Nutrients
·
2023
·Vol. 15
·期 5
·1090
·
IF 5.9
Yunpeng Zhang,Shuang Liu,Jing Peng,Shifeng Cheng,Qingling Zhang,Nan Zhang,Zandong Zhou,Yue Zhang,Yang Zhao,Tong Liu
Mitochondria-dependent ferroptosis plays an important role in the pathogenesis of doxorubicin (DOX)-induced cardiotoxicity (DIC), which remains a clinical challenge due to the lack of effective interventions. Cerium oxide (CeO2), a representative nanozyme, has attracted much attention because of its antioxidant properties. This study evaluated CeO2-based nanozymes for the prevention and treatment of DIC in vitro and in vivo by adding nanoparticles (NPs), which were synthesized by biomineralization, to the culture or giving them to the mice, and the ferroptosis-specific inhibitor ferrostatin-1 (Fer-1) was used as control. The prepared NPs exhibited an excellent antioxidant response and glutathione peroxidase 4 (GPX4)-depended bioregulation, with the additional merits of bio-clearance and long retention in the heart. The experiments showed that NP treatment could significantly reverse myocardial structural and electrical remodeling, and reduce myocardial necrosis. These cardioprotective therapeutic effects were associated with their ability to alleviate oxidative stress, mitochondrial lipid peroxidation, and mitochondrial membrane potential damage, with a superior efficiency to the Fer-1. The study also found that the NPs significantly restored the expression of GPX4 and mitochondrial-associated proteins, thereby restoring mitochondria-dependent ferroptosis. Therefore, the study provides some insights into the role of ferroptosis in DIC. It also shows that CeO2-based nanozymes could be a promising prevention and treatment candidate as a novel cardiomyocyte ferroptosis protector to mitigate DIC and improve prognosis and quality of life in cancer patients.Keywords:doxorubicin-induced cardiomyopathy;ferroptosis;mitochondria;nanozyme;oxidative stress;biomineralization
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INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2023
·
IF 8.2
Shihuai Li,Yunan Qing,Yan Lou,Ruiyan Li,Hao Wang,Xingyue Wang,Boda Ying,Xiongfeng Tang,Yanguo Qin
Removing residual tumor cells around bone tissue and promoting bone defect repair pose significant challenges after osteosarcoma resection. Herein, we designed an injectable multifunctional hydrogel therapeutic platform for synergistic photothermal chemotherapy of tumors and promoting osteogenesis. In this study, the black phosphorus nanosheets (BPNS) and doxorubicin (DOX) were encapsulated in an injectable chitosan-based hydrogel (BP/DOX/CS). The BP/DOX/CS hydrogel exhibited excellent photothermal effects under NIR irradiation due to incorporating BPNS. The prepared hydrogel has good drug-loading capacity and can continuously release DOX. In addition, K7M2-WT tumor cells are effectively eliminated under the combined effect of chemotherapy and photothermal stimulation. Furthermore, the BP/DOX/CS hydrogel has good biocompatibility and promotes osteogenic differentiation of MC3T3-E1 cells by releasing phosphate. In vivo results also confirmed that the BP/DOX/CS hydrogel can be injected at the tumor site to eliminate the tumor efficiently without systemic toxicity. This easily prepared multifunctional hydrogel with a synergistic photothermal-chemotherapy effect has excellent potential for clinically treating bone-related tumors.
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