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Controlled Release of doxorubicin from Electrospun MWCNTs/PLGA Hybrid Nanofibers

Chinese Journal of Polymer Science 2016年第9期34卷 1047-1047,1048-1059页

作者： Rui-ling Qi Xue-jiao Tian 郭睿 Yu Luo Ming-wu Shen Jian-yong Yu 史向阳 State Key Laboratory for Modification of Chemical Fibers and Polymer Materials Key Laboratory of Textile Science &Technology Ministry of Education College of Textiles Donghua University Department of Textile Engineering Henan Institute of Engineering College of Chemistry Chemical Engineering and Biotechnology Donghua University

In this study, multiwalled carbon nanotubes （MWCNTs） were used to encapsulate a model anticancer drug, doxorubicin （Dox）. Then, the drug-loaded MWCNTs （Dox/MWCNTs） with an optimized drug encapsulation percentage were mixed with poly（lactide-co-glycolide）（PLGA） polymer solution for subsequent electrospinning to form drug-loaded composite nanofibrous mats. The structure, morphology, and mechanical properties of the formed electrospun Dox/PLGA, MWCNTs/PLGA, and Dox/MWCNTs/PLGA composite nanofibrous mats were characterized using scanning electron microscopy （SEM）, Fourier transform infrared spectroscopy, and tensile testing. In vitro viability assay and SEM morphology observation of mouse fibroblast cells cultured onto the MWCNTs/PLGA fibrous scaffolds demonstrate that the developed MWCNTs/PLGA composite nanofibers are cytocompatible. The incorporation of Dox-loaded MWCNTs within the PLGA nanofibers is able to improve the mechanical durability and maintain the three-dimensional structure of the nanofibrous mats. More importantly, our results indicate that this double-container drug delivery system （both PLGA polymer and MWCNTs are drug carriers） is beneficial to avoid the burst release of the drug and able to release the antitumor drug Dox in a sustained manner for 42 days. The developed composite electrospun nanofibrous drug delivery system may be used as therapeutic scaffold materials for post-operative local chemotherapy.

关键词： Electrospun nanofibers Carbon nanotubes doxorubicin Controlled release.

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Aptamer-coded DNA nanoparticles for targeted doxorubicin delivery using pH-sensitive spacer

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Frontiers of Chemical Science and Engineering 2017年第4期11卷 529-536页

作者： Pengwei Zhang Junxiao Ye Ergang Liu Lu Sun Jiacheng Zhang Seung Jin Lee Junbo Gong Huining He Victor C. Yang . State Key Laboratory of Chemical Engineering School of Chemical Engineering and Technology Tianjin University Tianjin 300072 China.. Tianjin Key Laboratory on Technologies Enabling Development of Clinical Therapeutics and Diagnostics (Theranostic) Tianjin Medical University Tianjin 300072 China.. Department of Pharmacy Ewha Womans University Seoul 120-750 Korea.. Department of Pharmaceutical Sciences College of Pharmacy University of Michigan MI 48109-1065 USA

An anticancer drug delivery system consisting of DNA nanoparticles synthesized by rolling circle amplification （RCA） was developed for prostate cancer membrane antigen （PSMA） targeted cancer therapy. The template of RCA was a DNA oligodeoxynucleotide coded with PSMA-targeted aptamer, drug-loading domain, primer binding site and pH-sensitive spacer. Anticancer drug doxorubicin, as the model drug, was loaded into the drug-loading domain （multiple GC-pair sequences） of the DNA nanoparticles by intercalation. Due to the integrated pH-sensitive spacers in the nanoparticles, in an acidic environment, the cumulative release of doxorubicin was far more than the cumulative release of the drug in the normal physiological environment. In cell uptake experi- ments, treated with doxorubicin loaded DNA nanoparti- cles, PSMA-positive C4-2 cells could take up more doxorubicin than PSMA-null PC-3 cells. The prepared DNA nanoparticles showed the potential as drug delivery system for PSMA targeting prostate cancer therapy.

关键词： aptamer DNA nanoparticles rolling circleamplification doxorubicin drug delivery pH sensitive

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Ratiometric delivery of doxorubicin and berberine by liposome enables superior therapeutic index than Doxil?

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Asian Journal of Pharmaceutical Sciences 2020年第3期15卷 385-396页

作者： Ruoshi Zhang Yingxi Zhang Yue Zhang Xin Wang Xuanming Gao Yuyan Liu Xuanbo Zhang Zhonggui He Dun Wang Yongjun Wang Wuya College of Innovation Shenyang Pharmaceutical UniversityShenyang 110016China Department of Pharmaceutics Shenyang Pharmaceutical UniversityShenyang 110016China Key Laboratory of Structure-Based Drug Design and Discovery of Ministry of Education Shenyang Pharmaceutical UniversityShenyang 110016China

Although the appearance of Doxil alleviated the cardiotoxicity of DOX, the progression-free survival of patients was not prolonged compared with traditional medication regimens, and side effects such as hand-foot syndrome has occurred. In order to solve this dilemma, we have designed a novel co-delivery strategy to construct a co-loaded liposome of berberine(BER) and doxorubicin(DOX), which was called Lipo Be Do. The optimal synergistic ratio of the two drugs was screened by cell cytotoxicity experiments in vitro, and the optimal attenuation ratio was further determined by in vivo cardiac H&E staining pathological sections. The optimal combination treatment caused a robust increase in apoptotic cells of 4T1, as compared to drug alone treatment. The prepared co-loaded liposome, Lipo Be Do, had high encapsulation efficiency and good stability. The nanoliposome carrier controlled the biological fate of the drugs and maintained a pre-defined optimal ratio in vivo. The Lipo Be Do significantly inhibited tumor growth in 4T1 murine mammary carcinoma model compared with Doxil(P < 0.05), and completely overcame the myocardial rupture toxicity caused by Doxil in mice. Our co-loaded liposome delivery platform technology provided a new direction for the clinical treatment of triple-negative breast cancer and the safe application of DOX.

关键词： Berberine doxorubicin Nanoliposomes Remote loading Combination therapy Cardiotoxity

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Co-delivery of doxorubicin and quercetin via mPEG-PLGA copolymer assembly for synergistic anti-tumor efficacy and reducing cardio-toxicity

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Science Bulletin 2016年第21期61卷 1689-1698页

作者： Waseem Akhtar Qureshi Ruifang Zhao Hai Wang Tianjiao Ji Yanping Ding Ayesha Ihsan Ayeesha Mujeeb Guangjun Nie Yuliang Zhao CAS Key Laboratory for Biomedical Effects of Nanomaterialsand Nanosafety Center for Excellence in Nanoscience NationalCenter for Nanoscience and Technology Beijing 100190 China Department of Biomedical Engineering The Ohio StateUniversity Columbus OH 43210 USA National Institute for Biotechnology and Genetic Engineering(NIBGE) P.O. Box 577 Faisalabad Pakistan

橡黄素(Que ) 是自然多功能的 bioflavonoid，并且为减少不利副作用并且提高化学疗法的药的反肿瘤功效显示出大潜力。然而，它的临床的申请在生理的系统由于很低的溶解度和结构的不稳定性被限制。此处，我们共同交付由开发 amphiphilic... 详细信息

橡黄素(Que ) 是自然多功能的 bioflavonoid，并且为减少不利副作用并且提高化学疗法的药的反肿瘤功效显示出大潜力。然而，它的临床的申请在生理的系统由于很低的溶解度和结构的不稳定性被限制。此处，我们共同交付由开发 amphiphilic 聚合物包括的 biocompatible nanocarrier 的恐水病的橡黄素和吸水的 doxorubicin (纪录影片) ， methoxy poly (乙烯乙二醇) 并且 poly (D， L-lactide-co-glycolide ) 分别地。反肿瘤和这个系统的预防功效被评估在细胞并且动物模型。我们说明的调查结果 Dox-Que nanoparticulate 明确的表达保护了正常脉管的 endothelial 房间免受免费的任何一个或 nanoparticulate 的伤害导致 doxorubicin 的 cytotoxicity 和增加的癌症房间死亡。与免费 doxorubicin 和它的 nanoformulation 相比，用我们的 nanosystem 的橡黄素和 doxorubicin 的合作交货 synergistically 禁止了肿瘤生长，当在浆液维持心脏的功能指示物的正常层次并且在心织物恢复组织病理学说的损坏时。这研究为提高反癌症药功效并且减少 nanoparticulate 表明有希望的策略正常纸巾上的导致化疗的毒性。

关键词：聚合 nanoparticles doxorubicin 橡黄素 Cardio 毒性癌症治疗

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MiR-34a overexpression enhances the inhibitory effect of doxorubicin on HepG2 cells

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World Journal of Gastroenterology 2019年第22期25卷 2752-2762页

作者： Shun-Zhen Zheng Ping Sun Jian-Ping Wang Yong Liu Wei Gong Jun Liu Department of Liver Transplantation and Hepatobiliary Surgery Shandong Provincial Hospital Affiliated to Shandong UniversityJinan 250021Shandong ProvinceChina Department of Clinical Laboratory Blood Station of JinanJinan 250021Shandong ProvinceChina

BACKGROUND Hepatocellular carcinoma(HCC) is the third leading cause of death from malignant tumors worldwide. More than 50% of HCC cases occur in China. The prognosis remains poor and overall efficacy is still unsatisfactory. Chemotherapy resistance is the most important reason for the poor outcome. Much progress has been made in the study of chemotherapy resistance of HCC;however, the specific mechanisms of progression of HCC have still only been partially established.Therefore, the mechanism of chemotherapy resistance in HCC requires more research.AIM To investigate the effect of miR-34 a expression on the growth inhibition of HepG2 cells by doxorubicin.METHODS A recombinant lentiviral vector containing miR-34 a was constructed and transfected into HepG2 cells. The expression of miR-34 a was detected by reverse transcription-polymerase chain reaction(commonly known as RT-PCR) before and after transfection. Cells were exposed to 2 μM doxorubicin or phosphatebuffered saline before and after transfection. Cell viability in each group was detected by MTT assay, and cell cycle and apoptosis were detected by flow cytometry. Changes in expression levels of phospho(p)-p53, sirtuin(SIRT) 1,cyclin D1, cyclin-dependent kinase(CDK) 4, CDK6, BCL-2, multidrug resistance protein(MDR) 1/P glycoprotein(P-gp), and AXL were detected by Western blotting.RESULTS Recombinant lentiviral vector LV-hsa-mir-34 a was successfully constructed by restriction endonuclease digestion and sequencing. RT-PCR showed that expression of miR-34 a in HepG2 cells was significantly upregulated after transfection(P doxorubicin(P doxorubicin(P < 0.01). The apoptosis rate of HepG2 cells was increased after upregulation of miR-34 a, and became

关键词： miR-34a doxorubicin Hepatocellular carcinoma HepG2 cells Growth inhibition

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Idarubicin vs doxorubicin in transarterial chemoembolization of intermediate stage hepatocellular carcinoma

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World Journal of Gastroenterology 2020年第3期26卷 324-334页

作者： Gael Stephane Roth Yann Teyssier Melodie Abousalihac Arnaud Seigneurin Julien Ghelfi Christian Sengel Thomas Decaens Clinique Universitaire d’Hepato-Gastroenterologie et Oncologie Digestive CHU Grenoble-AlpesGrenoble 38043France Facultede Medicine Universite Grenoble-AlpesDomaine de la MerciLa Tronche 38700France Institute for Advanced Biosciences-INSERM U1209/CNRS UMR 5309/Universite Grenoble-Alpes Site Santé-Allée des AlpesLa Tronche 38700France Clinique Universitaire de Radiologie et Imagerie Médicale CHU Grenoble-AlpesGrenoble 38043France Departement de Sante Publique-CHU Grenoble-Alpes Grenoble 38043France Department of Hepatology and Gastroenterology Grenoble-Alpes University HospitalGrenoble 38043France

BACKGROUND Liver cancer is the fifth most common cancer and the second cause of cancerrelated deaths worldwide.Transarterial chemoembolization(TACE)is the best treatment of intermediate hepatocellular carcinoma(HCC).doxorubicin is the most commonly used drug despite a low level of evidence.AIM To compare the objective response rate of idarubicin-based TACE(Ida-TACE)against doxorubicin-based TACE(Dox-TACE)in intermediate stage HCC.METHODS Between January 2012 and December 2014,all patients treated with TACE at our academic hospital were screened.Inclusion criteria were patients with Child-Pugh score A or B,a performance status below or equal to 1,and no prior TACE.Either lipiodol TACE or drug-eluting beads TACE could be performed with 10 mg of idarubicin or 50 mg of doxorubicin.Each patient treated with idarubicin was matched with two doxorubicin-treated patients.The TACE response was assessed by independent radiologists according to the mRECIST criteria.RESULTS Sixty patients were treated with doxorubicin and thirty with idarubicin.There were 93%and 87%of cirrhotic patients and 87%and 70%of Child-Pugh A in the doxorubicin and idarubicin groups,respectively.The median number of HCC per patient was two in both groups with 31%and 26%of single nodules in doxorubicin and idarubicin groups,respectively.Objective response rate after first TACE was 76.7%and 73.3%(P=0.797)with 41.7%and 40.0%complete response in doxorubicin and idarubicin groups,respectively.Progression-free survival was 7.7 mo in both groups,and liver transplant-free survival was 24.9 mo and 21.9 mo in doxorubicin and idarubicin groups,respectively.Safety profiles were similar in both groups,with grade 3-4 adverse events in 35%of Dox-TACE and 43%of Ida-TACEs.CONCLUSION Ida-TACE and Dox-TACE showed comparable results in terms of efficacy and safety.Ida-TACE may represent an interesting alternative to Dox-TACE in the management of patients with intermediate stage HCC.

关键词： Hepatocellular carcinoma Transarterial chemoembolization Idarubicin doxorubicin Intermediate stage

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Targeted combination therapy for glioblastoma by co-delivery of doxorubicin,YAP-siRNA and gold nanorods

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Journal of Materials Science & Technology 2021年第4期63卷 81-90页

作者： Lihuang Li Qiuyan Guo Yanxiu Liu Mindan Lu Jun Yang Yunlong Ge Qiang Zhang Benqiang Sun Xiumin Wang Li Liang-cheng Lei Ren Key Laboratory of Biomedical Engineering of Fujian Province University/Research Center of Biomedical Engineering of Xiamen Department of BiomaterialsCollege of MaterialsXiamen UniversityXiamen 361005China School of Pharmaceutical Sciences Fujian Provincial Key Laboratory of Innovative Drug Target ResearchXiamen UniversityXiamen 361102China Department of Neurosurgery Xiang’an Hospital of Xiamen UniversitySchool of MedicineXiamen UniversityXiamen 361102China Stomatological Hospital of Xiamen Medical College Xiamen 361105China State Key Lab of Physical Chemistry of Solid Surfaces Xiamen UniversityXiamen 361005China

The combination of brain targeting drug delivery systems and multi-modal intervention pose a promising therapeutic approach for glioblastoma therapy.In this study,we developed an angiopep-2 peptide modified cationic liposome loaded with doxorubicin,YAP-siRNA and gold nanorods(D/R@Ang2-Lip+Au)simultaneously,which has high encapsulating efficiency for doxorubicin(95.4%)and effective binding of siRNA at N/P ratio of 20:1.The fluorescence imaging and flow cytometry analysis revealed high cellular uptake of D/R@Ang2-Lip+Au.Real-time quantitative polymerase chain reaction and western blot analysis indicated that D/R@Ang2-Lip+Au could effectively inhibit the expression of YAP protein.In vitro and in vivo studies showed that D/R@Ang2-Lip+Au had the ability to target glioblastoma cells,and achieved better anti-proliferative effects compared with non-targeted D/R@Lip+Au.Moreover,in vivo experiment demonstrated that D/R@Ang2-Lip+Au was able to cross the blood-brain barrier,and combination therapy could significantly inhibit tumor growth.Therefore,the multifunctional D/R@Ang2-Lip+Au might provide a novel approach for effectively delivery of DOX,YAP-siRNA and AuNRs into the glioblastoma cells simultaneously and exerting synergistic therapeutic effects.

关键词： doxorubicin glioblastoma simultaneous

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A microRNA-21-responsive doxorubicin-releasing sticky-flare for synergistic anticancer with silencing of microRNA and chemotherapy

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Science China Chemistry 2021年第6期64卷 1009-1019页

作者： Min Hong Hongxiao Sun Qiangqiang Yang Shuang Cheng Shuxian Yu Shuhua Fan Chuan Li Cheng Cui Weihong Tan School of Chemistry and Chemical Engineering Liaocheng UniversityLiaocheng 252059China School of Agriculture Liaocheng UniversityLiaocheng 252059China Molecular Science and Biomedicine Laboratory State Key Laboratory of Chemo/Biosensing and ChemometricsCollege of Chemistry and Chemical EngineeringCollege of Life SciencesCollaborative Innovation Center for Chemistry and Molecular MedicineHunan UniversityChangsha 410082China Department of Pharmacy Tai’an Municipal HospitalTai’an 271000China

A sticky-flare gold nanoparticle probe(AuNP-probe)is designed by the combination of locked nucleic acid functionalized silencing of microRNA technology for intracellular microRNA-21(miRNA-21)sensitively detecting,fluorescence imaging,localizing and silencing.The limit of detection is as low as 0.01 n M.Overexpressed miRNA-21 in cancer cells serves as endogenous drug release stimuli to trigger the release of probe-loaded doxorubicin(Dox),which soon translocates into cell nuclei.This multifunctional Dox-loaded AuNP-probe(Dox-AuNP-probe)could induce cancer cell apoptosis effectively through the synergistic effect of gene silencing and chemotherapy.This Dox-AuNP-probe exhibits superior drug potency compared to free Dox molecules,with a cell inhibition rate of 57%(but only 20%for Dox)to wild-type cancer cells and 30%(but 0%for Dox)to drug-resistent cancer cells after 72 h,and this strategy not only has the function of sensing,but also can effectively bypass drug resistance.In MCF-7 xenograft tumor-bearing mice,the Dox-AuNP-probes show greater inhibition for tumor tissues than miRNA-21 targeted AuNP-probes(Targeting-AuNP-probe)or free Dox molecules.Therefore,the Dox-AuNP-probe represents a promising nanotheranostic platform for future applications in cancer molecular imaging and therapy,especially providing a potential strategy to treat resistant cancers.

关键词： gold nanoparticle probe silencing microRNA-21 doxorubicin controlled-release synergistic anticancer

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Efficiency against multidrug resistance by co-delivery of doxorubicin and curcumin with a legumain-sensitive nanocarrier

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Nano Research 2018年第7期11卷 3619-3635页

作者： Sen Lin Peiling Xie Mengmeng Luo Qing Li Ling Li Jinzhao Zhang Qinxiang Zheng Hao Chen Kaihui Nan School of Ophthalmology & Optometry and Eye Hospital Wenzhou Medical University Wenzhou 325027 China Wenzhou Institute of Biomatefials and Engineering Chinese Academy of Science Wenzhou 325000 China School of Biomedical and Engineering Wenzhou Medical University Wenzhou 325027 China

Multidrug resistance proteins （MDRPs）, which are implicated in the mediation of multidrug resistance in tumors, represent the main obstacle to successful chemotherapy. As curcurnin （Cur） exerts inhibitory effects on both the expression and function of MDRPs, a nanocarrier for the co-delivery of Cur and doxorubicin （DOX） was prepared to overcome MDR tumors through their synergistic effects. Owing to the overexpression of legumain in tumors, the release profile of DOX from this nanocarrier was designed to be legumain modulated, which was achieved by bridging DOX to a basic material （chitosan） with a legumain- sensitive peptide. Compared with nanoparticles that only contain DOX, the coadministration of DOX and Cur significantly inhibited multidrug resistance （P 〈 0.05） in a multidrug-resistant cancer cell model （MCF-7/ADR cell line）, with cytotoxicity to normal cells （L929 cell line）. Such inhibition could be ascribed to the increased DOX accumulation in the MCF-7/ADR nucleus. The co-delivery system exhibited good anticancer effects through prolonged circulation time, improved tumor-targeting efficiency, elevation of the tumor inhibition activity, and the suppression of MDRP expression. These data revealed the enormous potential of this co-delivery system for cancer therapy, especially in the later stages where multidrug resistance may develop.

关键词： legumain doxorubicin curcumin co-delivery nanoparticle multidrug resistance

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Development of CaP nanocomposites as photothermal actuators for doxorubicin delivery to enhance breast cancer treatment

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Journal of Materials Science & Technology 2021年第4期63卷 73-80页

作者： Jie Liu Li Li Run Zhang Zhi Ping Xu Australian Institute for Bioengineering and Nanotechnology The University of QueenslandSt LuciaQLD4072Australia

Breast cancer is the most common one in women worldwide and doxorubicin(Dox)is one of the most commonly used and effective drugs for breast cancer treatment.Unfortunately,Dox-based chemotherapy faces irreversible cardiotoxicity and unsatisfactory therapy efficiency.It is desirable to devise Dox nanoformulations with less adverse effects and greater therapeutic efficacy for this cancer treatment.In this work,a multifunctional calcium phosphate nanoformulation(ICG-Dox/DNA@CaP)was developed by co-loading Dox/DNA complexes and indocyanine green(ICG)molecules for photothermal therapy(PTT)-enhanced chemotherapy.In this nanocomposite,using DNA as Dox carrier facilitated Dox loading into the CaP matrix,and significantly reduced Dox leakage as well as cytotoxicity in comparison with that of free Dox in physiological medium(pH 7.4).In specific,ICG-Dox/DNA@CaP only released Dox in a weakly acidic nuclease-containing environment,such as tumor microenvironment and endosome/lysosome.Moreover,Dox/DNA complexes exhibited synergistic interactions with ICG-based photothermal effect on tumor cell apoptosis in this ICG-Dox/DNA@CaP nanocomposite.This work has demonstrated a new strategy to combine FDA-approved therapeutics(Dox and ICG)in CaP-based nanomaterials for reduced cytotoxicity and enhanced therapeutic effect,and provided a new way to engineer CaP carriers as multifunctional delivery systems for clinical anti-cancer therapy.

关键词： chemotherapy doxorubicin breast

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