Materials Today Communications
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2022
·
IF 3.662
Hua Yuan,Liming Zhou,Zhiwen Qi,Changwei Zhang,Chengzhang Wang
This study focuses on the development of a new preparation method of solanesol derivatives for their effective use as drug carriers. The current preparation methods for solanesol derivatives generally suffer from poor accessibility and low yields of the target products, which affect the further development of their products. To address this issue, a solanesol-based poly (glutamic acid) (Sol-PEG-PGA) was first designed on the basis of the click reaction between alkynyl-functionalized solanesol and amino-polyethylene glycol (PEG)-azide, followed by a coupling reaction with poly (glutamic acid). The introduced polyethylene glycol and poly (glutamic acid) conferred amphipathic properties on solanesol. Sol-PEG-PGA possessed a suitable lipid-water partition coefficient of 1.01 and water contact angle of 55° and could self-assemble into spherical micelles with an average diameter of 74.0 ± 3.5 nm to load doxorubicin (DOX) via hydrophobic interaction, with a loading capacity of 27.7 ± 1.2 %. Besides, Sol-PEG-PGA micelle exhibited excellent stability before and after loading DOX under the dilution of 1000 times and could be stored stably at room temperature for 15 days. The DOX loaded into Sol-PEG-PGA could be released by acid induction, with a cumulative release of 84.8 ± 2.5 % at pH 5.0. Furthermore, in vitro cytotoxicity assay, the normal cells NIH/3T3 treated with Sol-PEG-PGA maintained relatively high viability of 95.0% compared to that of free DOX at 320 µg/mL, verifying its good biocompatibility. The DOX loaded into Sol-PEG-PGA possessed a high-efficiency anticancer activity compared to free DOX, with an inhibition rate of 99.2 ± 1.6 % against tumor cells 4T1, suggesting the potentials of Sol-PEG-PGA for drug delivery applications. This new preparation method is expected to provide a new strategy for constructing various functional carriers from solanesol derivatives.
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COLLOIDS AND SURFACES B-BIOINTERFACES
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2023
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IF 5.8
Danyang Chen,Xiangbo Ma,Jingjing Zhu,Yong Wang,Shuai Guo,Jianglei Qin
Self-healing hydrogels have shown great application potential in drug delivery for anti-tumor therapy and tissue engineering. In this research, Doxorubicin (DOX) was coupled onto the oxidized pectin (pec-Ald) to prepare DOX grafted pec-AD and used to fabricate self-healing hydrogel for lung cancer therapy combined with novel herbal medicine extract limonin targeting lung cancer cells. The hydrogel was prepared with P(NIPAM 195 - co -AH 54 ) cross-linking and the hydrazone bond cross-linked hydrogel showed good mechanical property and self-healing behavior. With pectin composition , the hydrogel was still biodegradable catalyzed by enzyme and in vivo. The hydrogel formed fast fit for injectable application and the hydrogel itself showed moderate lung cancer inhibition activity. With limonin loading, the hydrogel showed synergistic lung cancer therapy with the tumor growth greatly inhibited. The covalent coupling of DOX and loaded limonin in the hydrogel decreased in vivo toxicity and the hydrogel degraded on time. With biodegradability and improved lung cancer therapy efficiency, this DOX grafted self-healing hydrogel could find great potential application in cancer therapy in near future.
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AIP Advances
·
2023
·Vol. 13
·期 11
·
IF 1.6
Liu Jinhua,Zhu Guoren,Liu Yuanan,Wang Xiaohui
The combined treatment method integrated photothermal therapy (PTT) with chemotherapy is extremely promising owing to the synergistic therapeutic effect as compared to single PTT or chemotherapy. To facilitate more novel and facile photothermal-chemotherapy drugs as well as promote controllable combination therapy, we have developed a mild and facile method to fabricate polymer polypyrrole (PPy)-doxorubicin (DOX) nanoparticles (NPs) as pH-responsive drug nanocarriers for synergistic photothermal-chemotherapy. In the nanoplatform, poly-L-lysine (PLL)-modified PPy serves as the photothermal material, and (DOX) molecules are adopted as the chemotherapy agent. Based on the cross-linking reaction of glutaraldehyde, DOX molecules are flexibly and efficiently assembled on the surface of PLL-modified PPy NPs. The obtained PPy-DOX NPs possess high photothermal effect, superior loading capacity of DOX, and controlled drug release behavior. The combination photothermal-chemotherapy based on PPy-DOX NPs has significantly enhanced the antitumor therapy effect. In general, the designed PPy-DOX NPs may be a potential drug delivery nanoplatform for cancer combination therapy.
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PHYTOMEDICINE
·
2023
·
IF 7.9
Xiangyun Li,Taoli Sun,Jiaqin Liu,Shanshan Wei,Yuanying Yang,Jian Liu,Bikui Zhang,Wenqun Li
Background Doxorubicin (Dox), a chemotherapeutic agent known for its efficacy, has been associated with the development of severe cardiotoxicity, commonly referred to as doxorubicin-induced cardiotoxicity (DIC). The role and mechanism of action of phloretin (Phl) in cardiovascular diseases are well-established; however, its specific function and underlying mechanism in the context of DIC have yet to be fully elucidated. Objective This research aimed to uncover the protective effect of Phl against DIC in vivo and in vitro , while also providing a comprehensive understanding of the underlying mechanisms involved. Methods DIC cell and murine models were established. The action targets and mechanism of Phl against DIC were comprehensively examined by systematic network pharmacology, molecular docking, transcriptomics technologies, transcription factor (TF) prediction, and experimental validation. Results Phl relieved Dox-induced cell apoptosis in vitro and in vivo . Through network pharmacology analysis, a total of 554 co-targeted genes of Phl and Dox were identified. Enrichment analysis revealed several key pathways including the PI3K-Akt signaling pathway, Apoptosis, and the IL-17 signaling pathway. Protein-protein interaction (PPI) analysis identified 24 core co-targeted genes, such as Fos, Jun, Hif1a, which were predicted to bind well to Phl based on molecular docking. Transcriptomics analysis was performed to identify the top 20 differentially expressed genes (DEGs), and 202 transcription factors (TFs) were predicted for these DEGs. Among these TFs, 10 TFs (Fos, Jun, Hif1a, etc.) are also the co-targeted genes, and 3 TFs (Fos, Jun, Hif1a) are also the core co-targeted genes. Further experiments validated the finding that Phl reduced the elevated levels of Hif3a (one of the top 20 DEGs) and Fos (one of Hif3a's predicted TFs) induced by Dox. Moreover, the interaction between Fos protein and the Hif3a promoter was confirmed through luciferase reporter assays. Conclusion Phl actively targeted and down-regulated the Fos protein to inhibit its binding to the promoter region of Hif3a, thereby providing protection against DIC.
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MOLECULAR AND CELLULAR BIOCHEMISTRY
·
2023
·
IF 4.3
Lu Yanyu,Min Qianqian,Zhao Xiaoyan,Li Li,Zhao Guojun,Dong Jianzeng
Eupatilin is a pharmacologically active flavonoid with a variety of biological activities, such as anticancer, anti-inflammatory, antioxidant, neuroprotective, anti-allergic and cardioprotective effects. However, whether eupatilin has protective effects on doxorubicin-induced cardiotoxicity remains unknown. Thus, this study aimed to investigate the role of eupatilin in doxorubicin-induced cardiotoxicity. Mice were exposed to a single dose of doxorubicin (15 mg/kg) to generate doxorubicin-induced cardiotoxicity or normal saline as a control. To explore the protective effects, mice were intraperitoneally injected with eupatilin daily for 7 days. Then, we examined the changes in cardiac function, inflammation, apoptosis, and oxidative stress to evaluate the effects of eupatilin on doxorubicin-induced cardiotoxicity. Additionally, RNA-seq analysis was introduced to explore the potential molecular mechanisms. Eupatilin ameliorated doxorubicin-induced cardiotoxicity by attenuating inflammation, oxidative stress, and cardiomyocyte apoptosis and ameliorated doxorubicin-induced cardiac dysfunction. Mechanistically, eupatilin activated the PI3K-AKT signaling pathway, as evidenced by RNA-seq analysis and Western blot analysis. This study provides the first evidence that eupatilin ameliorates doxorubicin-induced cardiotoxicity by attenuating inflammation, oxidative stress, and apoptosis. Pharmacotherapy with eupatilin provides a novel therapeutic regimen for doxorubicin-induced cardiotoxicity.
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NEW JOURNAL OF CHEMISTRY
·
2023
·Vol. 47
·期 26
·12431-12444
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IF 3.3
Hailiang Chen,Chenyu Liu,Simiao Yu,Hengjun Zhou,Farishta Shafiq,Weihong Qiao
Polyethylene glycol (PEG), which can impart long cycling performance to drug carriers, has been commonly used for drug carrier modification. However, PEG modification impedes cellular uptake of drug carriers and intracellular release of drugs, a problem known as the “PEG dilemma” that limits its application. In this study, we designed and synthesized mPEG-NCH-DOB molecules with acid-sensitive hydrazone bonding for the responsive removal of PEG. Drug-loaded lipid PHDGX for doxorubicin (DOX) delivery was obtained by compounding mPEG-NCH-DOB with lipid DOPG, which possess the capability for long cycling, and acid-sensitive PEG-removal to accelerate drug release and enhance cellular uptake. mPEG-NCH-DOB could reach 50% fracture rate after 24 h at pH 5.0. The cytotoxicity assay and flow cytometry (FCM) results showed that PHDGX could enter A549/ADR cells more easily than free DOX at low DOX concentrations and has stronger anti-cancer ability. Through a confocal laser-scanning microscopy (CLSM) study, PHDGX was found to enter the nucleus of A549/ADR cells more easily than free DOX at the same time point, which indicated that PHDGX could overcome the DOX resistance of A549/ADR at low DOX concentrations. The 3D tumor microsphere (MC) growth inhibition assay showed that PHDGX not only has the best MC inhibition ability but also has better MC penetration ability than free DOX. Therefore, this drug-loaded liposome has good stability under conventional conditions and responsive PEG removal in the tumor acid environment, offering a potential strategy for utilizing PEG in drug carrier modification and overcoming tumor resistance to free drugs.
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Cancers
·
2023
·Vol. 15
·期 6
·1724
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IF 5.2
Khalil Ur Rahman,Shuo Yang,Nasir Azam,Zhen Yuan,Jiawen Yu,Chunhui Zhao,Bin Feng
Simple SummaryBreast cancer is a disease that begins in the cells of the breast. Although it is most common in women, it can also occur in men, though this is rare. Early detection and treatment are crucial to improving outcomes and survival rates. Risk factors include age, family history, certain gene mutations, prior history of breast cancer, exposure to estrogen, and lifestyle habits like alcohol consumption and inactivity. Symptoms include changes in the skin on the breast, such as dimpling, lumps or thickening, changes in size or shape, and discharge from the nipple. Diagnosis is often made through a clinical breast exam, mammogram, biopsy, and possibly additional imaging tests. Treatment options include surgery, chemotherapy, radiation therapy, hormone therapy, and targeted therapy. The choice of treatment method depends on the stage and characteristics of cancer.AbstractBreast cancer is considered the solid tumor most sensitive to chemotherapy. However, it can become resistant to various chemotherapeutic drugs, including doxorubicin, which triggers cell death by intercalation between DNA bases, free radical formation, and topoisomerase II inhibition. When drug resistance develops, several miRNAs are dysregulated, suggesting that miRNAs may play a significant role in resistance formation. In the current study, we investigated how doxorubicin sensitivity of breast cancer cells is affected by miR-153-3p and its target gene. The MTT method was used to determine the chemo-sensitizing effect of miR-153-3p on doxorubicin in MCF-7 and MDA-MB-231 cell lines. Results of Western blot and dual luciferase confirmed that miR-153-3p targets KIF20A and decreases its expression. Transwell and flow cytometry experiments showed that miR-153-3p and doxorubicin together had higher effects on MCF-7 and MDA-MB-231 cell proliferation, migration, and invasion, as well as increasing apoptosis and arresting cells in the G1 phase. Proteins related to apoptosis and the cell cycle exhibited the same tendency. Intracellular vesicle formation was inhibited and RAB26 was also downregulated by treatment with miR-153-3p alone or in combination with doxorubicin. Doxorubicin’s ability to suppress tumors may be enhanced by miR-153-3p, according to in vivo studies. According to our findings, miR-153-3p has a direct effect on KIF20A and may regulate the formation of intracellular vesicles, which in turn makes breast cancer cells more susceptible to doxorubicin.Keywords:miR-153-3p;chemosensitivity;breast cancer;doxorubicin;KIF20A
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CARBOHYDRATE POLYMERS
·
2023
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IF 11.2
Fangzhou He,Conghua Xie,Xiaojuan Xu
Breast cancer is one of the most threatening cancers that poses a great risk to women's health . The anti-tumor drug doxorubicin (DOX) is one of commonly used drugs in the treatment of breast cancer. However, the cytotoxicity of DOX has always been an urgent challenge to be solved. In this study, we report an alternative drug delivery system delivering DOX for reducing its physiological toxicity by using the yeast β-glucan particle (YGP) with a hollow and porous vesicle structure. Briefly, amino groups were grafted onto the surface of YGP with the silane coupling agent, then the oxidized hyaluronic acid (OHA) was attached by Schiff base reaction to get HA-modified YGP ( [email protected] =C-HA), finally DOX was encapsulated into [email protected] =C-HA to get DOX-loaded [email protected] =C-HA ( [email protected] =C-HA/DOX). In vitro release experiments exhibited the pH-responsive DOX release from [email protected] =C-HA/DOX. Cell experiments displayed that [email protected] =C-HA/DOX had good killing effect on both MCF-7 and 4T1 cells and could be internalized into these cells through CD44 receptors, showing targetability to cancer cells. Furthermore, [email protected] =C-HA/DOX could effectively inhibit tumor growth and reduce the physiological toxicity of DOX. Thus, the YGP-based vesicle provides an alternative strategy for lowering the physiological toxicity of DOX in the medical treatment of breast cancer.
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COLLOID AND POLYMER SCIENCE
·
2023
·Vol. 301
·期 8
·879-891
·
IF 2.4
Li Danyang,Xu Wenshuang,Liu Hui
Stimuli-responsive hydrogel could respond rapidly to environmental changes, whereas the limitation of gel scale usually led to a single route of drug delivery and restricted application. Herein, a pH and temperature dual responsive nanogel CS/P(MAA-co-NIPAM) was successfully prepared by radical polymerization. The change of both turbidity and hydration diameter at different conditions indicated that the nanogel possessed obvious pH and temperature sensitive properties. Specifically, the hydration diameters of the nanogel were 234 nm at T = 20 °C and 145 nm at T = 45 °C. The schematic flowable characteristic by injection experiment indicated that CS/P(MAA-co-NIPAM) might have the potential application possibility of injectable drug delivery. In addition, with doxorubicin as the model drug, the drug loading efficiency of the nanogel was 84.00% and the maximum release efficiency reached 66.30% at pH = 2.0 & T = 20 °C. The nanogel was able to realize drug delivery process in physiological environment according to in-vitro controlled releasing experiments.
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ONCOLOGY REPORTS
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2019
·Vol. 42
·期 1
·313-320
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IF 3.041
Xuan‑Chen Tao,Xin‑Yu Zhang,Shi‑Bo Sun,De‑Quan Wu
MicroRNAs (miRNAs) are a class of short noncoding RNAs that negatively regulate gene expression and act as oncogenes or tumor suppressors. Numerous miRNAs have been reported be associated with the occurrence and development of gastric carcinoma (GC). For instance, miR‑92a has been observed to be overexpressed in GC; however, the precise mechanisms underlying the role of miR‑92a in GC and its role in clinical therapy require further investigation. In the present study, it was reported that miR‑92a expression was significantly upregulated in GC tissues compared with in adjacent tissues. Additionally, suppression of miR‑92a significantly reduced SGC7901 cell viability as demonstrated by a Cell Counting Kit‑8 and colony formation assays. Suppression of miR‑92a inhibited SGC7901 cell proliferation as determined by Ki‑67 immunofluorescence staining, and the expression levels of proliferating cell nuclear antigen, cyclin dependent kinase (CDK)4 and CDK6, and increased that of p53. In addition, we reported that suppression of miR‑92a induced apoptosis in SGC7901 cells. Furthermore, bioinformatics analysis identified that ING2 as a potential target of miR‑92a. Downregulation of miR‑92a significantly increased ING2 expression at the mRNA and protein levels. A dual‑luciferase reporter assay validated a direct binding site of miR‑92a on ING2. In addition, SGC7901 cells with suppression of miR‑92a were more sensitive to doxorubicin treatment. Knockdown of miR‑92a reduced the half‑maximal inhibitory concentration of doxorubicin from 147.6 nM to 82.1 nM in SGC7901 cells. Knockdown of miR‑92a also reduced SGC7901 cell survival under doxorubicin stimulation. Furthermore, SGC7901 cells with suppression of miR‑92a harbored a greater number of DNA damage foci upon doxorubicin treatment compared with in control cells. The findings of the present study revealed that miR‑92a contributes to cell proliferation, apoptosis and doxorubicin chemosensitivity in GC cells, which suggests a potential therapeutic strategy for the treatment of GC.
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INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
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2018
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IF 3.909
Lili Chen,Yuanyuan Zheng,Longbao Feng,Zonghua Liu,Rui Guo,Yuanming Zhang
The aim of this work was to examine the formation and properties of a novel polyelectrolyte complex of drug carrier system for the delivery of doxorubicin (DOX), which consists of hyaluronic acid (HA) coated hydrophobically modified chitosan (CS). Various batches of polyelectrolyte complexes with the molar ratio of deoxycholic acid (DCA) and chitosan (CS) of 0.1, 0.2, 0.3 were prepared, and were termed as CS-DCA 10 , CS-DCA 20 , and CS-DCA 30 respectively. The samples were characterized by Fourier transform infrared (FTIR) spectroscopy, X-ray diffraction (XRD), Transmission electron microscopy (TEM), nuclear magnetic resonance hydrogen spectrum ( 1 H NMR) and dynamic light scattering (DLS). Particle sizes of synthesized polyelectrolyte complex nanoparticles (PCNs) were found to be in the range of 280–310 nm, larger than those of uncoated nanoparticles (~150 nm). The PCNs have large zeta potentials (about 26 mV) which make them stable and no sizes' change was determined. DOX could be easily incorporated into the PCNs with encapsulation efficiency (56%) and kept a sustained release manner without burst effect when exposed to PBS (pH 7.4) at 37 °C. Overall, these findings confirmed the potential of these PCNs for drug carrier and prolonged and sustained delivery in the bloodstream.
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ORGANIC & BIOMOLECULAR CHEMISTRY
·
2019
·Vol. 17
·期 15
·3853-3860
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IF 3.49
Leixia Mei,Keming Xu,Ziran Zhai,Suyun He,Tingting Zhu,Wenying Zhong
Drug incorporation in hydrogels often brings undesirable effects on the stability or mechanical properties of the system. To address this problem, we report the design and synthesis of a RGD-derived peptide conjugate (1-RGDH) for its co-assembly with a commonly used chemotherapeutic drug, doxorubicin (DOX), that formed electrostatic interactions with the 1-RGDH peptide and reinforced the supramolecular network of nanofibers within the matrix of the hydrogel. The hybrid hydrogel demonstrated excellent viscoelastic and shear-thinning properties that greatly facilitated the development of injectable drug delivery systems. Furthermore, it demonstrated a unique pH responsive release of DOX under weakly acidic conditions, paving ways for the controlled release of drug cargos in a typical tumor microenvironment with mild acidity. Finally, the DOX-incorporated hydrogel exhibited a superior anti-tumor efficacy in non-small-cell lung cancer cells A549 compared to the aqueous solution of free DOX, with an integrin receptor-mediated endocytosis pathway revealed for the cellular uptake of DOX-incorporated nanofibers.
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