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Preparation and functional characterization of tumor-targeted folic acid-chitosan conjugated nanoparticles loaded with mitoxantrone

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Journal of Central South University 2015年第9期22卷 3311-3317页

作者：王炜童春义刘星言李涛刘斌熊炜 Dongguan Research Center Guangdong Medical College College of Biology Hunan University Department of Ophthalmology and Eye Research Center The 2nd Xiangya Hospital Central South University

Folic acid conjugated chitosan was prepared by cross-linking reaction with 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide hydrochloride(EDC), and then used as a template to prepare folic acid-chitosan(FA-CS) conjugated nanoparticles and load mitoxantrone nanoparticles(FA-CSNP/MTX). Drug dissolution testing, CCK-8 method, and confocal microscopy were used to detect their controlled-release capability in different situations and the specific uptake by HONE1 cells. The experimental results show that the nanoparticles have uniform size distribution of 48-58 nm. The highest encapsulation rate of the particles on mitoxantrone hydrochloride(MTX) is(77.5±1.9)%, and the drug loading efficiency is(18.4±0.4)%. The sustained release effect, cell growth inhibition activity and targeting effect of the FA-CS/MTX nanoparticles are good in artificial gastric fluid and intestinal fluid. It is demonstrated that the FA-CSNP system is a potentially useful system for the targeted delivery of anticancer drug MTX.

关键词： folic acid chitosan nanoparticles mitoxantrone tumor targeting

Electrochemical Behavior of mitoxantrone and Its Determination at a Pt/C Implanted Modified Microelectrode

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Chemical Research in Chinese Universities 2004年第1期20卷 103-107页

作者： QIANYong-gui SUNZi-jie HUJing-bo LUYi-qiang LIQi-long DepartmentofChemistry BeijingNormalUniversityBeijing100875P.R.China DepartmentofChemistry BeijingUniversityofScienceandTechnologyBeijing100083P.R.China

In a 0.02 mol/L Na_2HPO_4-KH_2PO_4(PBS) buffer solution(pH=6.82), the electrochemical behavior of mitoxantrone was studied by linear-sweep voltammetry and cyclic voltammetry at a Pt/C ion implantation modified microelectrode. A sensitive reduction peak was observed. The peak potential was \{-0.72 V\}(***), the peak current was proportional to the concentration of mitoxantrone within the ranges of 7.0×10 -8—9.0×10 -7 mol/L and 1.0×10 -6—2.4×10 -5 mol/L, with a detection limit of 4.0×10 -8 mol/L. The linear correlation coefficients were 0.9994 and 0.9992, respectively. This method has been applied to the direct determination of mitoxantrone in simulated urine. The recoveries were in the range from 96.2% to 105.9%. The reduction process was a quasi-reversible one with adsorptive characteristics at the Pt/C microelectrode. The electrode reaction rate constant k_s and the electron transfer coefficient α of the system were determined to be 4.5 and 0.65 s -1, respectively. The experiments showed that Pt element had surely been implanted into the surface of the carbon fiber, and the atomic Pt improved the electrocatalytic activity. The Pt/C microelectrode had a good stability and reproducibility.

关键词： mitoxantrone Electrochemical behavior Ion implantation Modified microelectrode

Interaction Between mitoxantrone Metal Complex and Titan Yellow by Resonance Rayleigh Scattering Spectra and Its Analytical Application

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Chemical Research in Chinese Universities 2009年第3期25卷 291-296页

作者： HU Rong YANG Qiong ZHANG Shu-ran YANG Ji-dong School of Chemistry and Chemical Engineering Southwest University Chongqing 400715 P. R. China Department of Chemistry and Environment Science Yangtze Normal University Chongqing 408100 P. R. China

In a pH 2.4 Britton-Robinson buffer medium, the anthracycline antibiotics mitoxantrone（MXT） could react with metal ions such as Pd（Ⅱ）, Co（Ⅱ） and Cu（Ⅱ） to form 1：2（molar ratio） cationic chelates, which further reacted with the anionic dye titan yellow to form 1：2 ternary ion-association complexes by electrostatic interaction. As a result, the intensity of resonance Rayleigh scattering（RRS） was enhanced greatly. These RRS spectral characteristics of various metal ion systems were similar, and the maximum RRS wavelengths were all located at 454 nm. But the increments of RRS intensities were different in the series of Pd（Ⅱ）〉Co（Ⅱ）〉Cu（Ⅱ）. The enhanced RRS intensities were proportional to the concentration of MXT in a range of 0.03-2.4μg/mL and the detection limit（3σ） was 0.009μg/mL for the Pd（Ⅱ） system. In this study, the optimum conditions of the reactions and the effects of foreign substances were investigated, in addition, the composition and reaction mechanism of ion-association complexes were discussed. Thus a highly sensitive, simple and rapid method is proposed for the determination of MXT in urine and serum samples.

关键词： Resonance Rayleigh scattering mitoxantrone Metal ion Titan yellow

Study on the anticarcinogenic effect and acutetoxicity of liver-targeting mitoxantrone-nanoparticles

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World Journal of Gastroenterology 1999年第6期5卷 511-514页

作者： ZHANG Zhi Rong, HE Qin, LIAO Gong Tie and BAI Shao Huai 华西医科大学四川成都 610041 华西医科大学四川成都

AIM To study the anticarcinogenic effect and acute toxicity of liver targeting mitoxantrone nanospheres. METHODS The anticarcinogenic effect of mitoxantrone polybutylcyanoacrylate nanoparticles (DHAQ PBCA NP) was investigated by using heterotopic and orthotopic transplantation models of human hepatocellular carcinoma (HCC) in nude mice and was compared with mitoxantrone (DHAQ) and doxorubicin (ADR). The acute toxicity of DHAQ PBCA NP lyophilized injection in mice was also studied. RESULTS The tumor inhibition rates of ADR, DHAQ, DHAQ PBCA NP to orthotopically transplanted HCC were 60 07%, 67 49% and 99 44%, respectively, but regard to heterotopically transplanted HCC, these were 80 03%, 86 18% and 92 90%, which were concordant with the results acquired by mitosis counting and proliferating cell nuclear antigen (PCNA). After iv administration to mice with DHAQ PBCA NP, the LD 50 was 16 9*!mg/*!kg ± 3 9*!mg/*!kg , no obvious local irritation was observed and there was no significant damage to the structure of liver cells, and that of the heart, spleen and kidneys. CONCLUSION The effect of DHAQ PBCA NP was significantly higher than that of DHAQ and ADR in the anti orthotopically transplanted HCC and the acute toxicity was relatively low.

关键词： mitoxantrone nanospheres toxicity neoplasm transplantation nude mice

Mitochondrion targeting peptide-modified magnetic graphene oxide delivering mitoxantrone for impairment of tumor mitochondrial functions

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Chinese Chemical Letters 2021年第3期32卷 1220-1223页

作者： Hangqi Zhu Bing Zhang Nali Zhu Mingchun Li Qilin Yu Key Laboratory of Molecular Microbiology and Technology Ministry of EducationDepartment of MicrobiologyCollege of Life SciencesNankai UniversityTianjin 300071China College of Chemistry State Key Laboratory of Elemento-Organic ChemistryNankai UniversityTianjin 300071China Collaborative Innovation Center of Chemical Science and Engineering(Tianjin) Tianjin 300072China

In this study,we prepared mitochondrion targeting peptide-grafted magnetic graphene oxide(GO)nanocarriers for efficient impairment of the tumor *** two-dimensional GOMNP-MitP nanosheets were synthesized by grafting magnetic y-Fe_(2)O_(3)to the surface of GO,followed by covalent modification of mitochondrion targeting peptide(MitP).GOMNP-MitP exhibited the high capacity of loading the anticancer drug mitoxantrone(MTX),and preferentially targeted the tumor *** the aid of alternating magnetic field(AMF),the MTX-loading GOMNP-MitP released MTX to the mitochondria,severely impairing mitochondrial functions,including attenuation of ATP production,decrease in mitochondrial membrane potential(MMP),and further leading to activation of *** study realized high-efficient mitochondrion-ta rgeting drug delivery for anticancer therapy by twodimensional nanoplatforms.

关键词： Magnetic graphene oxide Nanocarrier Mitochondrion-targeting peptide mitoxantrone Cancer therapy

Comparison of mitoxantrone in Combination with Intermediate-dose Cytarabine versus High-dose Cytarabine as Consolidation Therapies for Young Non-APL Acute Myeloid Leukemia Patients with Favorable and Intermediate Cytogenetics

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Journal of Huazhong University of Science and Technology(Medical Sciences) 2018年第1期38卷 51-57页

作者： Ji-hao ZHOU Hai-qing LIN Qi SHEN Li-na HU Guo-qiang LI Xiong-fei SUN Xin-you ZHANG Department of Hematology The Second Clinical Medical College of Jinan University （Shenzhen People＇s Hospital） Jinan University Shenzhen 518020 China

In this study,we compared the efficacy of mitoxantrone in combination with intermediate-dose cytarabine（HAM） with that of high-dose cytarabine alone（Hi DAC） as consolidation regimens in non-acute promyelocytic leukemia（APL） acute myeloid leukemia patients with favorable and intermediate cytogenetics.A total of 62 patients from Shenzhen People＇s Hospital were enrolled in this *** patients enrolled received standard induction chemotherapy and achieved the first complete remission（CR1）.In these patients,24 received Hi DAC and 38 received HAM as *** median relapse free survival（RFS） and overall survival（OS） were similar between these two consolidation *** in subgroup analysis according to risk stratification,the combination regimen conferred no benefit in longterm outcome in patients with favorable or intermediate ***,in patients receiving HAM regimen,the lowest neutrophil count was lower,neutropenic period longer,neutropenic fever rate higher,and more platelet transfusion support was *** group also tended to have higher rate of sepsis than Hi DAC *** to our results,we suggest that combination treatment with mitoxantrone and intermediate-dose cytarabine has limited value as compared to Hi DAC,even in young non-APL AML patients with favorable and intermediate cytogenetics.

关键词： cytarabine mitoxantrone consolidation acute myeloid leukemia cytogenetics

Clinical Observation of FMD Regimen:Fludarabine,mitoxantrone,Dexamethasone,in Treatment of Non-Hodgkin's Lymphoma

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Chinese Journal of Clinical Oncology 2008年第6期5卷 433-436页

作者： Shuqing Lu Jianmin Wang Xianmin Song Li Chen Weiping Zhang Jun Hou Xiaoqian Xu Chongmei Huang Jianmin Yang Department of Hematology Changhai Hospital Second Military Medical UniversityShanghai 200433 China

OBJECTIVE To evaluate the clinical effectivity and toxicity of the regimen FMD （fludarabine, mitoxantrone, dexamethasone） in patients with non-Hodgkin＇s lymphoma. METHODS Thirty-two patients, twenty-four of whom had indolent B-cell lymphoma, 6 peripheral T-cell lymphoma, two diffuse large B-cell lymphoma, received FMD. Treatment comprised： fludarabine 25-30 mg/m^2 days 1-3, mitoxantrone 8-10 mg/m^2 day 1, and dexamethasone 20-30 mg/m^2 days 1-5. At the same time, patients received prophylaxis against conditional infection with trimethoprim-sulfamethoxazole, fluconazole, acyclovir and immunoglobulin. RESULTS Of the thirty-two patients treated, the complete response （CR） rate, partial response （PR） rate and overall response （OR） rate were 56.3%, 21.9% and 78.2% respectively. The CR and OR rate of 24 patients with indolent B-cell lymphoma were 66.7% and 88.3% respectively. Two of six patients with peripheral T-cell lymphoma were of complete response type and one was of partial response type. One of two patients with diffuse large B-cell lymphoma was partial response. The dominating toxicity was myelotoxicity and immunotoxicity. There was no treatment associated death in all patients treated with FMD. Grade 3-4 neutropenia occurred in 43.8% patients, 12.5% patients had infections and 9.3% developed grade 3-4 thrombocytopenia. At a median follow-up of 24 （5-54） months, the 2-year overall-survival rate and progression-free survival rate were （87.5 ± 1.4）% and （83.3 ± 1.6）% respectively. The 2-year OS and PFS rates of the indolent group were （93.75 ± 6.25）% and （87.5 ± 8.54）%. CONCLUSION FMD regimen was highly effective with low toxicity in the treatment of non-Hodgkin＇s lymphoma, especially in indolent B-cell lymphoma. It also helps to improve the prognosis even in some aggressive lymphoma, such as peripheral T cell lymphoma.

关键词： fludarabine mitoxantrone dexamethasone lymphoma non-Hodgkin's.

The synthesis of potential anticancer drugs related to mitoxantrone

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中国抗生素杂志 2001年第2期26卷 112-117页

作者： ZhengWei JamesLBloomer DepartmentofChemistry TempleUniversityPhiladelphiaPA19122U.S.A

ABSTRACT In an attempt at a rational design for anticancer drugs, two new potential anticancer compounds related to mitoxantrone were prepared. Compounds 4. 1.4-dihydroxy-6-aminoethyl-9.10-anthracenedione was synthesized in 6 steps starting with 4-methyl-phthalic acid, and compound 5, 2(4-aminobutyl)-l 4-dihvdroxv-9,10-anthracenedione was synthesized in 5 steps from N-3-bromopropylphthalimide.

关键词： Anticancer drugs mitoxantrone New compounds

Sensitive Voltammetric Determination of mitoxantrone by Using CS-Dispersed Graphene Modified Glassy Carbon Electrodes

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Advances in Chemical Engineering and Science 2012年第4期2卷 453-460页

作者： Bin Hong Qiong Cheng Department of biological and Chemical Engineering Jiaxing University Jiaxing China Department of Petrochemical Engineering Changzhou University Changzhou China

A novel CS-dispersed graphene modified glassy carbon electrode was fabricated. Study electrochemical characteristics of mitoxantrone in the CS-dispersed graphene modified electrode by cyclic voltammetry and other methods, by selecting and optimizing the various parameters to create a new electrochemical method for the determination of mitoxantrone. The linear range of the oxidation peak current is from 6×10–10 to 1 ×10–6 mol/l in this method, after 2.5 mins open-circuit accumulation, the limit of detection is 2×10–10 mol/l. After 10 parallel determinations, the relative standard deviation was 3.7% that the concentration of mitoxantrone was 1×10–8 mol/l. The modified electrode has been successfully applied for the assay of mitoxantrone in human urine samples.

关键词： mitoxantrone CS-Dispersed Graphene Modified Electrode Voltammetry