NANOTECHNOLOGY
·
2015
·Vol. 26
·期 39
·395602
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IF 3.821
Xiaoqing Yi,Quan Zhang,Hui Dong,Dan Zhao,Jia-qi Xu,Renxi Zhuo,Feng Li
In this paper, we first synthesized a novel disulfide-coupled bis-(cyclic carbonate) (TDCSS) monomer. After ring-opening co-polymerization (ROP) of TDCSS and trimethylene carbonate (TMC) initiated by mono-methoxyl poly(ethylene glycol), the crosslinked reduction-sensitive copolymer PEG-P(TMC-co-TDCSS) was obtained via a facile one-step procedure for efficient delivery of doxorubicin (DOX) into cancer cells. To serve as controls, PEG-P(TMC-co-TDCCC), which has an analogous structure without disulfide bond, and a linear polymer PEG-PTMC were also prepared. The copolymers could self-assemble to form nano-sized micelles in an aqueous solution. As compared to PEG-PTMC, crosslinked PEG-P(TMC-co-TDCSS) and PEG-P(TMC-co-TDCCC) showed lower CMC values and thus induced a much better micelle-forming ability. In vitro release studies revealed that the drug release behavior of DOX-loaded PEG-P(TMC-co-TDCSS) micelles, which could be accelerated in the presence of 10 mM dithiothreitol (DTT), showed a similar trend in the absence of DTT compared to DOX-loaded PEG-P(TMC-co-TDCCC) micelles. Furthermore, confocal laser scanning microscopy (CLSM) indicated that DOX-loaded PEG-P(TMC-co-TDCSS) micelles were efficiently internalized into HeLa cells, releasing DOX into the cytoplasm after which the drug finally entered the nuclei, while MTT assays also demonstrated potent cytotoxic activity against HeLa cells. DOX was mainly located in the cytoplasm for reduction-insensitive PEG-P(TMC-co-TDCCC) and PEG-PTMC controls.
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TALANTA
·
2025
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IF 6.1
Luke Wei,Yuxin Hu,Jiamin Wu,Jing Mao,Tianqin Yin,Jieqiong Qiu
Doxorubicin (DOX), a widely utilized chemotherapeutic antibiotic, increasingly threatens environmental and public health due to its persistence in marine ecosystems, bioaccumulation in organisms, and contamination of agricultural systems. In response to the urgent demand for effective DOX detection, we have developed a label-free fluorescent aptamer biosensor (FAB) that employs SYBR Green I (SG I)-mediated signal amplification. A key innovation in this design is the strategic fragmentation of the 41-mer complementary strand (CP) of the DOX aptamer into three 11-mer fragments. It significantly mitigates nonspecific SG I binding interference caused by the longer ssDNA CP, enhancing the fluorescence signal ratio (F dsDNA /F ssDNA ) from 4.6-fold to 12.6-fold. Upon DOX introduction, competitive binding between DOX, SG I, and DNA further suppresses background noise, yielding an exceptional fluorescence quenching ratio (F 0 /F) of 52.8. The optimized FAB demonstrates ultra-sensitive DOX detection, with a detection limit of 1.41 nM and a linear response between 1.41 nM and 300 nM. The recoveries of DOX spiked into pond water and drinking water samples ranged from 95.1% to 101.8%, with relative standard deviations (RSDs) below 3.46%, demonstrating negligible matrix effects and confirming the FAB method’s robustness for environmental monitoring applications. This strategy synergistically enhances signal transduction efficiency, and strengthens detection reliability, all while maintaining operational simplicity. As a result, this FAB for DOX detection holds transformative potential, poised to revolutionize biosensor technology in the fields of food safety, environmental monitoring, and biosecurity.
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Polymers
·
2018
·Vol. 10
·期 3
·326
·
IF 2.935
Feng Ji,Hong Sun,Zhihui Qin,Ershuai Zhang,Jing Cui,Jinmei Wang,Shuofeng Li,Fanglian Yao
Multifunctional drug carriers have great applications in biomedical field. In this study, we introduced both polydopamine (PDA) and zwitterionic polymer of poly(3-(3-methacrylamidopropyl-(dimethyl)-ammonio)propane-1-sulfonate) (PSPP) onto the surface of mesoporous silica nanoparticles (MSNs) to develop a novel nanoparticle (MSNs@PDA-PSPP), which was employed as a new kind of drug carrier for the delivery of doxorubicin (DOX). The PDA coating, as a gatekeeper, could endow the drug carrier with pH-sensitive drug release performance. The outermost PSPP layer would make the drug carrier possess protein resistance performance. The chemical structure and properties were characterized by Fourier transform infrared spectroscopy (FTIR), transmission electron microscopy (TEM), dynamic light scattering (DLS) and thermogravimetric analysis (TGA). MSNs@PDA-PSPP could keep good colloidal stability within 72 h in phosphate buffered saline (PBS) and protein solutions. Meanwhile, MSNs@PDA-PSPP exhibited a high drug loading for DOX. In vitro drug release experiments suggested MSNs-DOX@PDA-PSPP exhibited pH-dependent drug release behaviors. Besides, MSNs@PDA-PSPP had no cytotoxicity to human hepatocellular carcinoma cells (HepG2 cells) even at a concentration of 125 µg/mL. More importantly, cellular uptake and in vitro anticancer activity tests suggested that MSNs-DOX@PDA-PSPP could be taken up by HepG2 cells and DOX could be successfully released and delivered into the cell nuclei. Taken together, MSNs@PDA-PSPP have great potential in the biomedical field.
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JOURNAL OF COLLOID AND INTERFACE SCIENCE
·
2016
·
IF 3.782
Hui Zhang,Jiangkang Xu,Liang Xing,Jianbo Ji,Aihua Yu,Guangxi Zhai
Doxorubicin (DOX) is one of the most common chemotherapeutic agents for the treatment of various cancers, but its clinical usage is limited by dose-dependent cardiotoxicity. We have recently synthesized a series of Chondroitin sulfate/poly ( d , l -lactideco-glycolide) block copolymers (Chs- b -PLGA) with different length of hydrophobic block by an end-to-end coupling strategy. The structure of the amphiphilic block copolymers with low critical micelle concentration (∼28 mg/L) were confirmed by 1 H NMR. The copolymers could self-assemble into stable micelles in aqueous environment with homogeneous size distribution and negative zeta potential . The hemolytic study indicated their excellent blood compatibility and potential application for intravenous administration. DOX can be efficiently encapsulated by the Chs- b -PLGA micelles. The DOX-loaded micelles showed a sustained and pH dependent drug release behavior. The cytotoxicity assay showed no associated toxicity with blank micelles while concentration-related cell inhibition with DOX-loaded micelles. Moreover, fast cellular uptake of DOX-loaded micelles was observed by fluorescent microscope. In vivo pharmacokinetics study showed that the Chs- b -PLGA micelles could significantly prolong the blood circulation time of DOX. The maximum tolerated dose (MTD) of DOX-loaded micelles in Kunming mice was about 2-fold higher of the MTD of free DOX, indicating a high tolerance of the DOX-loaded micelles. In conclusion, the Chs- b -PLGA micelles would be a potentially useful drug delivery system for cancer therapy.
研究领域:
药剂学
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药物递送
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纳米医学
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高分子科学
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癌症治疗
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生物医学工程
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Redox Biology
·
2026
·
IF 16.2
Yan Chen,Bo Zhang,Yufan Wei,Yanfa Dai,Baoyue Zhang,Jing Li,Ke-Jia Wu,Ning Sun,Chenwen Shao
Doxorubicin (DOX)-induced cardiotoxicity remains a major limitation of cancer chemotherapy, largely due to the lack of sensitive approaches for early detection and effective cardioprotective interventions. This study investigated whether cysteine depletion represents an early redox event during DOX cardiotoxicity and evaluated a cysteine-activatable fluorescent probe, termed the cardiotoxicity-responsive cysteine probe (CCP), for in vivo redox imaging and therapeutic discovery. Cardiac imaging revealed a significant reduction in intracellular cysteine levels three weeks after DOX administration, preceding systolic dysfunction detected by echocardiography at four weeks. Mechanistically, cysteine depletion was accompanied by impaired glutathione-dependent antioxidant defense, iron accumulation, lipid peroxidation, and ferroptosis. Through probe-guided screening, gnetol (a naturally occurring polyphenolic stilbene) was identified as a potent regulator of intracellular cysteine homeostasis. Gnetol restored cysteine and glutathione levels, reduced lipid peroxidation, and suppressed ferroptosis by modulating the SMAD–hepcidin–FPN1 axis and preserving glutathione peroxidase 4 activity. In the mouse model of DOX-induced cardiomyopathy, gnetol significantly improved cardiac function, attenuated myocardial injury and fibrosis, and reduced oxidative stress without evident systemic toxicity. Collectively, these findings establish cysteine depletion as an early redox feature of DOX cardiotoxicity and demonstrate that cysteine-targeted redox imaging enables mechanism-guided discovery of cardioprotective agents. This study highlights gnetol as a promising ferroptosis-suppressing candidate and provides a mechanistic framework for early detection and intervention in redox-driven cardiac injury.
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NAUNYN-SCHMIEDEBERGS ARCHIVES OF PHARMACOLOGY
·
2026
·
IF 4
Liu Jie,Chen Jun,Zhang Lei,Xia Chunyong
Doxorubicin (DOX) efficacy in breast cancer is limited by dose-dependent cardiotoxicity and the development of multidrug resistance, while celastrol (Cel) suffers from poor solubility, low bioavailability and systemic toxicity. Their combination offers synergistic potential, but effective co-delivery remains challenging. We designed a protein-based nanoplatform via ferric ion-mediated biomimetic mineralization co-assembly of DOX, Cel, and human serum albumin (HSA) for enhanced antitumor therapy. HSA-Fe(III)-Cel-DOX nanoparticles were characterized by dynamic light scattering (DLS) and transmission electron microscopy (TEM). Drug loading and encapsulation efficiencies were determined by high-performance liquid chromatography (HPLC). In vitro drug release was evaluated with or without glutathione (GSH). Cytotoxicity against 4T1 murine breast cancer cells was assessed by CCK-8 assay. The optimized HSA-Fe(III)-Cel-DOX NPs (8 mM Fe 3 ⁺) exhibited uniform spherical morphology with an average diameter of approximately 64.6 nm and narrow size distribution (PDI = 0.103). The nanoparticles demonstrated exceptionally high drug encapsulation efficiencies (96.7 ± 1.9% for DOX and 94.5 ± 1.4% for Cel) and drug loading capacities (19.7 ± 0.5% for DOX and 17.3 ± 0.4% for Cel). The formulation exhibited excellent colloidal stability over 28 days of storage. In vitro release studies revealed remarkable GSH-responsive behavior, with cumulative release reaching 77.0 ± 3.3% for DOX and 64.0 ± 2.9% for Cel at 12 h under reducing conditions, while negligible release (< 5%) under non-reducing conditions was observed in the absence of GSH. Cytotoxicity assays demonstrated that HSA-Fe(III)-Cel-DOX NPs exerted significantly enhanced antitumor effect against 4T1 cells compared to free DOX or free Cel alone. At an equivalent DOX concentration of 0.5 μg/mL, the nanoparticles reduced cell viability to 29.2 ± 1.2%, substantially lower than free DOX (89.7 ± 2.0%) or free Cel (100.4 ± 2.2%). We successfully constructed a ferric ion-mediated biomimetic nanoplatform via co-assembly of DOX, Cel, and HSA. This nanoplatform offers facile preparation, excellent stability, GSH-responsive drug release, and significantly enhanced in vitro cytotoxicity, representing a promising strategy for synergistic breast cancer therapy.
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CARBOHYDRATE POLYMERS
·
2026
·
IF 13.2
Yangyi Chen,Yue Wei,Qiao Li,Huajuan He,Hui Chen,Huajing Zhang,Xiaoqing Rong,Xiao Liang,Shiyuan Lin,Wei Zhang
A kind of novel pyrimidine nucleoside (PYN) and silybin (SB) conjugated chitosan (CS) (PYN-CS-SB) polymer micelles were designed for enhancing the oral absorption of doxorubicin (DOX) via the nucleoside transporters located at intestinal epithelial cell. The four types of endogenous PYNs selected respectively as the ligands of the transporter, along with SB, were conjugated to CS. The PYN-CS-SB were synthesized and identified by 1 H NMR and FT-IR. The drug-loaded micelles were prepared by ultrasound-assisted self-assembly, and their predominant characteristics, including the microscopic well-dispersed and regular globular shapes with the small particle sizes of 143 nm - 170 nm and the high loading capacities of 9–12%, the amorphous form of DOX encapsulated in micelles, the low critical micelle concentration of 23.1–31.6 μg/ml, and extremely sustained in-vitro release, were shown. Among them, the desoxycytidine (DCD) conjugated micelles (DCD-CS-SB@DOX) exhibited the highest oral bioavailability of 391% versus DOX·HCl. The enhanced absorption based on the nucleoside transporter-mediation, and the dual inhibition of PYN-CS-SB micelles on P-gp efflux and CYP3A4 enzyme, was confirmed by cellular uptake, immunofluorescence, enzyme activity inhibition test. The findings showed the extensive potential of intestinal nucleoside transporter mediated PYN-CS-SB micelles in oral drug delivery.
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MACROMOLECULAR RESEARCH
·
2023
·Vol. 31
·期 3
·181-191
·
IF 2.4
Li Jiyu,Zhu Li,Wu Shuai,Wang Guixue,Chen Yidan,Wu Wei
Chemotherapy is the main strategy for inhibiting the tumor growth. However, during the therapy, the side effect of anti-cancer drug will injure normal cells. For reducing the toxic of the free drug, stimuli responsive nanoparticles (NPs) have been prepared base on the pathological acidic environment around tumor for safe and efficient anti-tumor applications. In this study, we fabricated the phenylboronic acid (PBA) modified monomethoxy polyethylene glycol (MEPG) for encapsulating doxorubicin (DOX NPs). In the drug delivery system (DDS), the pH-responsive boric ester could be stable during drug delivery, and enhance DOX rapidly release in tumor lesion under the acidic stimuli. In vitro studies further demonstrated that DOX NPs could efficiently endocytose by tumor cells, and exhibit the similar anti-tumor activity as the free DOX resulting from the pH-responsive drug release profiles under tumor acidic stimuli. In summary, DOX NPs could be a feasible candidate to improve the safe and efficient DOX delivery for improving the potential anti-tumor applications. Graphical abstract
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International Journal of Nanomedicine
·
2023
·
IF 8
Fang Li,Chunli Zheng,Junbo Xin,Fangcheng Chen,Hua Ling,Linlin Sun,Thomas J Webster,Xin Ming,Jianping Liu
A novel method was developed here to prepare albumin-based nanoparticles (NPs) for improving the therapeutic and safety profiles of chemotherapeutic agents. This approach involved crosslinking bovine serum albumin (BSA) using a Schiff base-containing vanillin, into NPs and loading doxorubicin (DOX) into the NPs by incubation. The resultant NPs (DOX-BSA-V-NPs) displayed a particle size of 100.5±1.3 nm with a zeta potential of −23.05±1.45 mV and also showed high drug-loading efficiency and excellent stability with respect to storage and temperature. The encapsulation of DOX into the BSA-V-NPs was confirmed by dynamic scanning calorimetry and Raman spectroscopy. DOX-BSA-V-NPs exhibited a significantly faster DOX release at pH 6.5 than pH 7.4, as well as in a solution with a higher glutathione concentration. In vitro studies showed that the cellular uptake of DOX-BSA-V-NPs was time-dependent, concentration-dependent, and faster than free DOX, while the cytotoxicity of DOX-BSA-V-NPs (IC50 value of 3.693 μg/mL) was superior to free DOX (IC50 value of 4.007 μg/mL). More importantly, DOX-BSA-V-NPs showed a longer mean survival time of 24.83 days, a higher tumor inhibition rate of 56.66%, and a decreased distribution in the heart than other DOX formulations in animal studies using a tumor xenograft model. Thus, the vanillin-based albumin NPs were shown here to be a promising carrier for tumor-targeted delivery of chemotherapeutic agents and, thus, should be further studied.
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International Journal of Nanomedicine
·
2023
·
IF 8
Kai Dong,Zhuang-Zhuang Zhao,Jian Kang,Lei-Ruo Lin,Wen-Ting Chen,Jin-Xi Liu,Xiang-Long Wu,Ting-Li Lu
Background Combined chemotherapy is often affected by the different physicochemical properties of chemotherapeutic drugs, which should be improved by the reasonable design of co-loaded preparations.Purpose A kind of simple but practical graphene oxide (GO) wrapped mesoporous silica nanoparticles (MSN) modified with hyaluronic acid (MSN@GO-HA) were developed for the co-delivery of cinnamaldehyde (CA) and doxorubicin (DOX), in order to enhance their combined treatment on tumor cells and reduce their application defects.Methods The MSNCA@GODOX-HA was constructed by MSNCA (loading CA via physical diffusion) and GODOX-HA (modified with HA and loading DOX via π–π stacking) through the electrostatic adsorption, followed by the physicochemical characterization, serum stability and in vitro release study. Cytotoxicity on different cells was detected, followed by the tumor cell uptake tests. The intracellular reactive oxygen species (ROS) changes, mitochondrial functions and activities of caspase-3/-9 in MCF-7 cells were also evaluated, respectively.Results The MSNCA@GODOX-HA nanoparticles kept stable in FBS solution and achieved pH-responsive release behavior, which was beneficial to increase the accumulation of CA and DOX in tumor cells to enhance the treatment. MSNCA@GODOX-HA exerted higher cytotoxicity to MCF-7 human breast cancer cells than H9c2 cardiac myocyte cells, which were not only attributed to the active targeting to tumor cells by HA, but also related with the activation of intrinsic apoptotic pathway in MCF-7 cells induced by CA, which was mediated by the specific ROS signal amplification and the interference with mitochondrial function. Moreover, the efficacy of DOX was also enhanced by the above process.Conclusion The establishment of the MSNCA@GODOX-HA nanoparticles played a role in promoting strengths and restricting shortcomings of CA and DOX, thereby exerting their function and achieving efficient treatment against cancer.
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International Journal of Nanomedicine
·
2023
·
IF 8
Hongxiang Wei,Jinyuan Chen,Shenglin Wang,Feihuan Fu,Xia Zhu,Chaoyang Wu,Zhoujie Liu,Guangxian Zhong,Jianhua Lin
Purpose The primary goal of the present study was to develop the nano-drug consisting of doxorubicin and exosome derived from mesenchymal stem cells, and to explore its effect on osteosarcoma in vitro.Methods The exosomes were isolated from bone marrow MSCs (BM-MSCs) by an Exosome Isolation Kit. The exosome-loaded doxorubicin (Exo-Dox) was prepared by mixing exosome with Dox-HCl, desalinizing with triethylamine and then dialyzing against PBS overnight. The nanoparticle tracking analysis (NTA) and transmission electron microscope (TEM) were used to characterize of the exosome and Exo-Dox. The cytotoxicity of Exo-Dox was determined by CCK-8 assay. Further, the cellular uptake of different drugs was analyzed using inverted fluorescence microscope and flow cytometry.Results The typical exosome structures can be observed by TEM. After loading with doxorubicin, its size is larger than free exosome. Compared with the free Dox, the prepared Exo-Dox showed enhanced cellular uptake efficiency and anti-tumor effect in osteosarcoma MG63 cell line but low cytotoxicity in myocardial H9C2 cell line.Conclusion The prepared Exo-Dox could be used as an excellent chemotherapeutic drug for treatment of osteosarcoma in vitro. Considering the tumor-homing feature of BM-MSCs, the Exo-Dox may be a good candidate for targeted osteosarcoma treatment in future study.
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JOURNAL OF ETHNOPHARMACOLOGY
·
2022
·
IF 5.195
Zhen Xue,Lingxin Zhuo,Bowen Zhang,Lingmeng Zhu,Xinran Xiang,Chunxia Zhang,Wenyuan Liu,Guangguo Tan,Wenting Liao
Ethnopharmacological relevance Qifu decoction (QFD) is a famous traditional Chinese medicine (TCM) composed of Astragali Radix (HuangQi) and Aconiti Lateralis Radix Praeparaia (Fuzi), which can alleviate doxorubicin (DOX)-induced cardiotoxicity (DIC). However, its protective mechanism remains obscured. Aim of the study The present study aimed to uncover the cardioprotective mechanism and the synergistic effect of QFD against DIC in mice. Materials and methods The cardioprotective activity of QFD against DIC was assessed by electrocardiogram, serum biochemical assays and histopathology. Mass spectrometry-based metabolomic approach was conducted to elucidate the preventive mechanisms of QFD, HuangQi decoction (HQD), and Fuzi decoction (FZD) against DIC. QFD, HQD, FZD-targeted metabolic pathways were identified and compared to investigate the synergistic mechanism of QFD by computational systems analysis. Quantitative real-time PCR (qRT-PCR) was further employed to validate the key metabolic pathways at the level of the gene. Results The electrocardiogram combined with the biochemical analysis and histopathology showed that the protection effects were sorted as QFD > HQD ≈ FZD. A total of 41 metabolites contributing to DIC were identified in the mice serum, among which 32, 12 and 10 metabolites were significantly reverted by QFD, HQD and FZD, respectively. Metabolic pathway analysis revealed that DOX perturbed 12 metabolic pathways, and QFD, HQD, and FZD-treated groups could significantly reverse 12, 7 and 6 metabolic pathways of these 12 metabolic pathways. Metabolic pathway and qRT-PCR revealed that QFD could protect DIC mainly by regulating energy metabolism, amino acids metabolism, arachidonic acid metabolism and glycerophospholipid metabolism, and HQD and FZD mutually reinforced each other. Conclusion These evidences revealed that QFD was a promising drug candidate for DIC by maintaining metabolic homeostasis. Meanwhile, this work provided a useful approach for evaluating the efficacy and the synergistic effects of TCMs against cardiomyopathy .
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