Frontiers in Oncology
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2022
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IF 5.738
Wu Fengjiao,Shao Rongrong,Zheng Peisen,Zhang Tingting,Qiu Chenyu,Sui Hehuan,Li Shaotang,Jin Libo,Pan Huanle,Jin Xiance,Zou Peng,Cui Ri,Xie Congying
Colon cancer is one of the most common cancer in the world. Doxorubicin (DOX) is a classical anti-tumor drug which widely used in treatment of cancers, however, high toxicity limited its further clinical application. Thus, it is urgent to find new drugs with low toxicity and high efficiency to treat colon cancer. Isoalantolactone (IATL), an isomeric sesquiterpene lactone isolated from the plant of inula helenium, has been reported to have anti-cancer activity against a variety of cancer cells. However, the function of IATL in colon cancer remains unclear. Here, we demonstrated that IATL inhibited colon cancer cell growth by increasing cellular reactive oxygen species (ROS) production. Further study showed that ROS accumulation contributed to DNA damage and JNK signaling pathway activation. In addition, we found that IATL markedly enhanced DOX-induced cell cytotoxicity in colon cancer cells. IATL in combination with DOX significantly increased the ROS production, induced DNA damage and activated JNK signaling pathway. Taken together, our data suggested that combined treatment with IATL and DOX may serve as a potential therapeutics for colon cancer.
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LUMINESCENCE
·
2022
·Vol. 37
·期 6
·868-875
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IF 2.613
Feifei Li,Pengfei Fan,Xinbei Chen,Xi Lin,Can Liu,Congcong Hu,Shengyuan Yang,Fubing Xiao
Sensitive detection of doxorubicin (DOX) is critical for clinical theranostics. A novel ratiometric fluorescence strategy based on the inner filter effect (IFE) has been established for the sensitive detection of DOX by designing a ratiometric fluorescence probe. In the presence of DOX, the fluorescence intensity of copper nanoclusters (CuNCs) at 485 nm decreases, and the fluorescence intensity of carbon dots at 560 nm increases. Therefore, DOX can be quantitatively detected by measuring the ratio of the fluorescence intensities at 560 and 485 nm ( F 560 / F 485 ). The F 560 / F 485 ratio exhibits a linear correlation with the DOX concentration in the range from 1.0 × 10 −8 M to 1.0 × 10 −4 M with the detection limit of 3.7 nM. Furthermore, this method was also successfully applied to the analysis of DOX in human plasma samples, affording an effective platform for drug safety management.
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EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
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2022
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IF 7.088
Yi Zhao,Yao Peng,Zhongzhen Yang,Jiaqi Lu,Ru Li,Yuesen Shi,Yaxin Du,Ze Zhao,Li Hai,Yong Wu
To synergistically treat glioma with a combination chemotherapy, we design and prepare novel cascade-targeted liposomes (Lip-TPGS) using glucose and triphenylphosphonium (TPP) as targeting moieties, which could intelligently deliver redox-sensitive doxorubicin (DOX) prodrugs (SDOX) and chemotherapeutic sensitizer lonidamine (LND). The pH-responsive ligand Chol-TPG modified by PEGylated glucose can overcome the blood-brain barrier and reach tumor cells. Combined with the modification of mitochondria targeting ligand (Chol-TPP), Lip-TPGS are endowed with pH-responsive charge regulation function and multi-stage targeting abilities. After triggered by the excessive glutathione in tumor cells, Lip-TPGS could sufficiently release the parent drugs DOX, which would significantly reduce side effects without compromising anti-glioma efficacy. Therefore, Lip-TPGS possess these characteristics: good pharmacokinetic behavior, superior brain targeting ability, specific tumor recognition and internalization capability, and strong endo/lysosome escaping and mitochondria targeting potential. Furthermore, Lip-TPGS exhibit significant advantages on anti-glioma by inhibiting proliferation, promoting apoptosis , inducing mitochondria dysfunction, inhibiting migration and invasion, prolonging the survival time, narrowing tumor areas, limiting lung metastasis , and reducing toxicity to normal organs. In summary, Lip-TPGS, with cascade targeting abilities from tissue/cell to organelle levels and highly controlled drug release properties, would become a promising drug delivery system for glioma treatment.
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Drug Design Development and Therapy
·
2022
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IF 4.319
Kamel S Ahmed,Shenhuan Liu,Jing Mao,Jie Zhang,Lipeng Qiu
Background The active-targeted drug delivery systems had attracted more and more attention to efficiently overcome multidrug resistance (MDR) in cancer treatments. The aim of the work was to develop a multifunctional nano-structured liposomal system for co-delivery of doxorubicin hydrochloride (DOX) and celecoxib (CEL) to overcome doxorubicin resistance in breast cancer.Methods A functional hybrid peptide (MTS-R8H3) with unique cellular penetrability, endo-lysosomal escape and mitochondrial targeting ability was successfully synthesized using solid phase synthesis technology. The peptide modified targeted liposomes (DOX/CEL-MTS-R8H3 lipo) for co-delivery of DOX and CEL were formulated to overcome the chemoresistance in MCF/ADR cells.Results DOX/CEL-MTS-R8H3 lipo showed nanosized shape and displayed high stability for one month. The cytotoxicity effect of the co-delivery of DOX and CEL through peptide modified liposomes had remarkable treatment efficacy on killing MCF/ADR cells. Targeted liposome exhibited greater cellular entry ability about 5.72-fold stronger than DOX solution. Moreover, as compared with unmodified liposomes, the presence of MTS-R8H3 peptide entity on liposome surface enhanced the mitochondrial-targeting ability and achieved effective reactive oxygen species (ROS) production with significant inhibition of P-gp efflux activity.Conclusion The study suggested that the DOX/CEL-MTS-R8H3 lipo is a promising strategy for overcoming drug resistance in breast cancer treatments with high targeting inhibition efficiency.
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Frontiers in Bioengineering and Biotechnology
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2022
·
IF 6.064
He Yiwei,Zhang Yuqing,Gong Yuanchuan,Zhang Zhewei,Xu Tiancheng,Tian Liqiang,Pan Ting,Yang Hong,Pan Hao,Kou Quanming,Wang Hao,Shao Guoliang
Currently, clinically available drug-loaded embolic microspheres have some shortcomings, such as being invisible with standard medical imaging modalities and only being able to carry positively charged drugs. The visualization of drug-loaded microspheres is very important for real-time monitoring of embolic position to improve the therapeutic effect. Meanwhile, the visualization of microspheres can enable postoperative reexamination, which is helpful for evaluating the embolization area and guiding the subsequent treatment. In addition, microspheres capable of loading different charged drugs can increase the choice of chemotherapeutic drugs and provide more possibilities for treatment. Therefore, it is of great importance to explore drug-loaded microspheres capable of multimodal imaging and loading drugs with different charges for transarterial chemoembolization (TACE) treatment of liver tumors. In our study, we designed a kind of nano-assembled microspheres (NAMs) that can realize computer X-ray tomography (CT)/magnetic resonance imaging (MRI)/Raman multimodal imaging, be loaded with positively and negatively charged drugs and test their imaging ability, drug loading and biological safety. The microspheres have strong attenuation performance for CT, high T2 relaxation for MRI and good sensitivity for surface enhanced Raman spectroscopy (SERS). At the same time, our microspheres can also load the positively charged drug, doxorubicin (DOX), and negatively charged drug Cisplatin. One gram of NAMs can hold 168 mg DOX or 126 mg Cisplatin, which has good drug loading and sustained-release capacity. Cell experiments also showed that the nano-assembled microspheres had good biocompatibility. Therefore, as multimodal developed drug loaded microspheres, nano assembled microspheres have great potential in TACE treatment of liver cancer.
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POLYMER TESTING
·
2022
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IF 4.931
Ruiling Xu,Junhui Sui,Mingda Zhao,Yuedi Yang,Lei Tong,Yongmei Liu,Yong Sun,Yujiang Fan,Jie Liang,Xingdong Zhang
Human epidermal growth factor receptor-2 (HER-2) positive breast cancer is highly invasive with poor clinical outcomes and high risk of recurrence. Here, trastuzumab functionalized pullulan-doxorubicin nanoparticles (Tz-P-Dox) were developed and characterized as a new anticancer formulation for active targeting HER-2 overexpression of breast cancer cells. The obtained nanoparticles had the hydrodynamic diameter of 66.7 ± 2.0 nm and PDI of 0.218 ± 0.012. And the in vitro results showed significant difference of cell uptake and cytotoxic effect between Tz-P-Dox and non-targeted P-Dox against HER-2 positive cell lines (BT474 and MCF-7 cells). However, the differences between Tz-P-Dox and P-Dox were not observed in HER-2 negative cell lines (MDA-MB-231 cells). These results suggested that trastuzumab functionalized nanoparticles had great potential to be considered as a candidate drug for HER-2 positive breast cancer treatment.
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高影响因子
PHYTOMEDICINE
·
2021
·
IF 5.34
Yang Zhang,Shan Liu,Jiu-Long Ma,Chen Chen,Peng Huang,Jia-Hua Ji,Di Wu,Li-Qun Ren
Background Doxorubicin (DOX) is a broad-spectrum anti-tumor drug that has been associated with cardiotoxicity. Plant extracts have been shown to confer protection against DOX-induced cardiotoxicity. Apocynum venetum L . belongs to the Apocynaceae family. Flavonoid extracted from Apocynum venetum L . possess various biological effects, such as lowering blood pressure levels, sedation, diuresis, anti-aging, and improving immunity. Purpose This study investigated the mechanism by which dry leaf extract of Apocynum venetum L. (AVLE) alleviates DOX-induced cardiomyocyte apoptosis. Methods HPLC-MS/MS and HPLC methods were used to analyze the components of AVLE. The effects of DOX and AVLE on apoptosis of H9c2 and HMC cells were assessed using the MTT assay. Calcein AM/PI, TUNEL, and flow cytometry were carried out to determine the effects of AVLE on DOX-induced apoptosis. The effect of AVLE on DOX-induced oxidative stress in cardiomyocytes was investigated using ELISA test. Mito-Tracker Red CMXRos, JC-1, and RT-qPCR assays were performed to evaluate the impact of AVLE on DOX-induced cardiomyocyte mitochondrial activity and membrane permeability. Western blot assay was carried out to determine the activation of multiple signaling molecules, including phosphorylated-protein kinase B (p-AKT), Cytochrome c, Bcl-2 family, and caspase family in the apoptosis pathway. The AKT inhibitor was used to block AKT/Bcl-2 signaling pathway to investigate the role of AKT in the protection conferred by AVLE against DOX-induced cardiotoxicity. Results A total of 8 compounds, including rutin, hyperoside, isoquercetin, unidentified compounds, myricetin, quercetin, quercetin-3-O-glucuronide and kaempferol, were detected in AVLE. Of note, DOX suppressed lactate dehydrogenase (LDH) levels, aggravated oxidative stress, and promoted cardiomyocyte apoptosis. It also upregulated the mRNA expression levels of voltage-dependent anion channel 1 (VDAC1), adenosine nucleotide transporter 1 (ANT1), and cyclophilin D (CYPD), while suppressing mitochondrial activity and mitochondrial membrane permeability. Treatment with DOX altered the expression levels of apoptosis-associated proteins, Bcl-2 and Bax. However, AVLE treatment alleviated DOX-induced effects on cardiomyocytes. In addition, application of AKT inhibitors promoted DOX-induced apoptosis and reversed the inhibitory effects of AVLE on DOX-induced apoptosis. Conclusions AVLE confer cardio protection by suppressing oxidative stress and apoptosis of cardiomyocytes via AKT/Bcl-2 signaling pathway.
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International Journal of Nanomedicine
·
2021
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IF 6.4
Ronghua Tan,Danlei Tian,Jiaoyan Liu,Congcong Wang,Ying Wan
Background Chemotherapeutic drugs used for tumor treatments often show limited efficiency due to their short lifetime, nonspecific delivery, and slow or insufficient intracellular drug release, and also, they can cause severe system or organ toxicity. The development of chemotherapeutic nanomedicines with high efficacy and satisfactory safety still remains a challenge for current tumor chemotherapy.Methods A novel type of conjugate was synthesized using hydroxyethyl starch (HES) as a carrier while binding doxorubicin (DOX) onto HES backbone through a pH/redox responsive linker containing both disulfide and hydrazone bonds in series. The built conjugates were self-assembled into nanoparticles (NPs) (HES-SS-hyd-DOX NPs) for achieving enhanced antitumor therapy and adequate safety.Results HES-SS-hyd-DOX NPs had a certain ability for the tumor-orientated drug accumulation and were capable of releasing DOX itself rather than DOX derivatives. It was found that the pH/redox responsive linkage enabled the NPs to achieve fast and sufficient intracellular drug release. Based on the tumor-bearing mouse model, antitumor results demonstrated that these NPs were able to inhibit the growth of the advanced tumors with significantly enhanced efficacy when compared to free DOX, and to those conjugate NPs containing only a single responsive or unresponsive bond. Besides, HES-SS-hyd-DOX NPs also showed adequate safety to the normal organs of the treated mice.Conclusion The pH/redox responsive linkage in HES-SS-hyd-DOX was found to play a critical role in mediating the drug accumulation and the fast and sufficient intracellular drug release. The HES-exposed surface of HES-SS-hyd-DOX NPs endowed the NPs with long circulation capability and remarkably reduced the DOX-induced side effects.
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ACS Applied Polymer Materials
·
2020
·
IF 0
Wei Zhang,Yi Li,Lanju Xu,Dou Wang,Jing Long,Meng Zhang,Yufei Wang,Yuxiao Lai,Xing-Jie Liang
Combination therapy based on a nanoscale drug delivery system (nDDS) shows great promise in cancer therapy. We report herein the development of a nanotherapeutic that combines photothermal therapy (PTT) and chemotherapy into one nanoformula to achieve combinatorial anticancer capacity. Near-infrared (NIR)-absorbing conjugated polymers (CPs) were used as the PTT agents and coloaded with chemotherapeutic drug doxorubicin (Dox) to afford the multifunctional delivery system DCP NPs. The strong NIR absorbance of CPs endows DCP NPs with excellent photothermal capacity and NIR laser triggered drug release property. The fluorescence of Dox was quenched after encapsulation because of the fluorescence resonance energy transfer (FRET) effect between Dox and CPs, which could be used to monitor the intracellular Dox release from DCP NPs. As a result of these properties, DCP NPs exhibited very potent anticancer capacity against osteosarcoma 143B cells. This study demonstrates the great potential of CPs-based nanotherapeutic for combined photothermal-chemotherapy to combat cancer.
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COLLOID AND POLYMER SCIENCE
·
2020
·Vol. 298
·期 3
·303-312
·
IF 1.536
Gao Feng,Wang Qiang,Yang Xiaochun
Synthesis of amphiphilic poly( β -amino esters) (PBAE) was optimized by stepwise feeding of monomers (PBAE-(P-H)) compared with one-pot synthesis (PBAE-(P&H)) based on poly(ethylene glycol) diacrylate (PEGDA) and 1,6-hexanediol diacrylate (HDDA). Interestingly, optimized synthetic PBAE-(P-H) had smaller critical micelle concentration (CMC) of 6.6 μg/mL on average than one-pot synthetic PBAE-(P&H) (10.4 μg/mL). Nanoparticles were prepared based on PBAE-(P-H) and PBAE-(P&H), respectively. PBAE-(P-H) nanoparticles exhibited more narrow size distribution (average size, 105.3 nm; PDI, 0.103) than PBAE-(P&H) nanoparticles (average size, 117.8 nm; PDI, 0.233) demonstrated by dynamic light scattering and transmission electron microscopy. Afterward, PBAE-(P-H) and PBAE-(P&H) nanoparticles were selected to further investigate the properties including charge conversion and pH responsiveness. Doxorubicin (DOX) was encapsulated into nanoparticles. DOX release in vitro was enhanced as the decrease of pH value. Furthermore, DOX-loaded PBAE-(P-H) and PBAE-(P&H) nanoparticles exhibited enhanced cytotoxicity and cellular uptake against HCT116 cells compared with DOX under tumor microenvironment.
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Materials Science & Engineering C-Materials for Biological Applications
·
2020
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IF 5.88
Yuanfeng Pan,Junren Liu,Kunni Yang,Pingxiong Cai,Huining Xiao
Nanogel based on polysaccharides has attracted the tremendous interest due to its unique performance as drug carrier for in vivo release. In this work, the multi-responsive nanogels were developed based on the tailor-modified sugarcane bagasse cellulose (SBC). In the presence of crosslinking agent cystamine bisacrylamide (CBA), the in-situ free radical copolymerization of methacrylated monocarboxylic sugarcane bagasse cellulose (MAMC-SBC) and N-isopropylacrylamide (NIPAM) in aqueous phase was conducted, thus leading to redox, pH and thermal-responsive nanogels. The results obtained from FT-IR, SEM and particle sizer showed that the nanogels were highly stable with the desired particle size ranging from 90 to 180 nm and contained targeted polymeric segments and linkage for multi-responsivity. Doxorubicin hydrochloride (DOX) as a model drug was effectively loaded into the nanogels, partly driven by strong electrostatic association; and the loading efficiency reached up to 82.7%. Moreover, the drug release could be readily manipulated by the addition of reducing agent, pH and temperature, which is attributed to the multi-responsive behavior of nanogels as carrier and synergetic effects. The performance of nanogels was also governed by the ratio of reactive MAMC-SBC and NIPAM during polymerization; and the ratio at 1:1(wt) led to the optimal structure of nanogels.
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Science Advances
·
2020
·Vol. 6
·期 18
·
IF 13.117
Chen-Cheng Xue,Meng-Huan Li,Yang Zhao,Jun Zhou,Yan Hu,Kai-Yong Cai,Yanli Zhao,Shu-Hong Yu,Zhong Luo
The rapid development of treatment resistance in tumors poses a technological bottleneck in clinical oncology. Ferroptosis is a form of regulated cell death with clinical translational potential, but the efficacy of ferroptosis-inducing agents is susceptible to many endogenous factors when administered alone, for which some cooperating mechanisms are urgently required. Here, we report an amorphous calcium carbonate (ACC)–based nanoassembly for tumor-targeted ferroptosis therapy, in which the totally degradable ACC substrate could synergize with the therapeutic interaction between doxorubicin (DOX) and Fe2+. The nanoplatform was simultaneously modified by dendrimers with metalloproteinase-2 (MMP-2)–sheddable PEG or targeting ligands, which offers the functional balance between circulation longevity and tumor-specific uptake. The therapeutic cargo could be released intracellularly in a self-regulated manner through acidity-triggered degradation of ACC, where DOX could amplify the ferroptosis effects of Fe2+ by producing H2O2. This nanoformulation has demonstrated potent ferroptosis efficacy and may offer clinical promise.
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