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Research of the influence of Doxorubicin loaded melanin particles on drug resistance of anaplastic thyroid cancer cells |
ZHANG Yuchun1,2 ZHANG Qing1 YANG Yu1 ZHAO Yijing1 WANG Kun1 MA Xianghua2 |
1.Department of Endocrinology, the Affiliated Jiangning Hospital of Nanjing Medical University, Jiangsu Province, Nanjing 210000, China;
2.Department of Endocrinology, the First Affiliated Hospital of Nanjing Medical University, Jiangsu Province, Nanjing 210000, China |
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Abstract Objective To research the influence of Doxorubicin loaded melanin nanoparticles (DOX-MNPs) on drug resistance of anaplastic thyroid cancer (ATC) cells. Methods Dopamine-melanin nanoparticles (MNPs) were synthesized as previously reported and Doxorubicin (DOX) was loaded onto MNPs. The loading efficiency and capacity of MNPs at different mass ratios of DOX to MNPs were determined by UV-Vis spectroscopy and the characterization of nanoparticles was acquired by transmission electron microscopy (TEM) and Brookhaven Zeta PALS analyzer. HTh74 and HTh74R cells were incubated with various concentrations of free DOX and DOX-MNPs (0, 10, 20, 40, 80, 160 mg/L). Cell viability was determined by MTT, and intracellular DOX fluorescent signal was determined by flow cytometry studies. Results The MNPs was successfully synthesized and the loading efficiency of DOX-MNPs decreased with the increasing mass ratio of DOX to MNPs. The loading efficacy peaked at 93.45% when the mass ratio was 0.167:1. At this mass ratio, the obtained DOX-MNPs had similar morphology to MNPs, and zeta potential and size distribution of DOX-MNPs were 13.79 mV and (241.1±4.8) nm. In HTh74R cells, when the concentration of DOX-MNPs was higher than 20 mg/L, the cell viability was significantly lower than that of the equivalent drug concentration (P < 0.05), and the uptake rate of DOX-MNPs was significantly higher than that of free DOX (P < 0.05). The degree of uptake was similar to that of HTh74 cells. Conclusion The cellular uptake capacity and therapeutic effect of the DOX-MNPs are significantly higher than those of free DOX at the same drug concentration in drug-resistant HTh74R cells.
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[1] Davies L,Welch HG. Increasing incidence of thyroidcancer in the United States,1973-2002 [J]. JAMA,2006,295(18):2164-2167.
[2] Haddad RI,Lydiatt WM,Ball DW,et al. Anaplastic Thyroid carcinoma,version 2.2015 [J]. J Natl Compr Canc Netw,2015,13(9):1140-1150.
[3] Nachalon Y,Stern-Shavit S,Bachar G,et al. Aggressive palliation and survival in anaplastic thyroid carcinoma [J]. JAMA Otolaryngol Head Neck Surg,2015,141(12):1128-1132.
[4] Xu X,Yang X,Zhao RN,et al. Comparison of ultrasonic features between anaplastic thyroid carcinoma and papillary thyroid carcinoma [J]. Zhongguo Yi Xue Ke Xue Yuan Xue Bao Acta Academiae Medicinae Sinicae,2015, 37(1):71-74.
[5] Lin RY.Thyroid cancer stem cells [J]. Nat Rev Endocrinol,2011,7(10):609-616.
[6] Molinaro E,Romei C,Biagini A,et al. Anaplastic thyroid carcinoma:from clinicopathology to genetics and advanced therapies [J]. Nat Rev Endocrinol,2017,13(11):644-660.
[7] Davis PJ,Incerpi S,Lin HY,et al. Thyroid hormone and P-glycoprotein in tumor cells [J]. Biomed Res Int,2015:168 427.
[8] Zheng X,Cui D,Xu S,et al. Doxorubicin fails to eradicate cancer stem cells derived from anaplastic thyroid carcinoma cells:characterization of resistant cells [J]. Int J Oncol,2010,37(2):307-315.
[9] Massart C,Poirier C,Fergelot P,et al. Effect of sodium butyrate on doxorubicin resistance andexpression of multidrug resistance genes in thyroid carcinomacell [J]. Anticancer Drugs,2005,16(3):255-261.
[10] Chen G,Xu S,Renko K,et al. Metformin inhibitsgrowth of thyroid carcinoma cells,suppresses self-renewalof derived cancer stem cells,and potentiates the effect ofchemotherapeutic agent [J]. J Clin Endocrinol Metab,2012,97(4):E510- E520.
[11] Zeng L,Pan Y,Tian Y,et al. Doxorubicin-Loaded NaYF4:Yb/Tm-TiO2 inorganic photosensitizers for nirtriggered photodynamic therapy and enhanced chemotherapy in drug-resistant breast cancerscancers [J]. Biomaterials,2015,57:93-106.
[12] Gao Y,Chen Y,Ji X,et al. Controlled intracellular release of doxorubicin in multidrug-resistant cancer cells by tuning the shell-pore sizes of mesoporous silica nanoparticles [J]. ACS Nano,2011,5(12):9788-9798.
[13] Cristiano MC,Cosco D,Celia C,et al. Anticancer activity of all-trans retinoic acid-loaded liposomes on human thyroid carcinoma cells [J]. Colloids Surf B Biointerfaces,2017,150:408-416.
[14] Gigliotti CL,Ferrara B,Occhipinti S,et al. Enhanced cytotoxic effect of camptothecin nanosponges in anaplastic thyroid cancer cells in vitro and in vivo on orthotopic xenograft tumors [J]. Drug Deliv,2017,24(1):670-680.
[15] Liu Y,Ai K,Liu J,et al. Dopamine-melanin colloidal nanospheres:an efficient near-infrared photothermal therapeutic agent for in vivo cancer therapy [J]. Adv Mater,2013,25(9):1353-1359.
[16] Wang X,Zhang J,Wang Y,et al. Multi-responsive photothermal-chemotherapy with drug-loaded melanin like nanoparticles for synergetic tumor ablation [J]. Biomaterials,2016,81:114-124.
[17] Fan Q,Cheng K,Hu X,et al. Transferring biomarker into molecular probe:melanin nanoparticle as a naturally active platform for multimodality imaging [J]. J Am Chem Soc,2014,136(43):15 185-15 194.
[18] Liopo A,Su R,Oraevsky AA. Melanin nanoparticles as a novel contrast agent for optoacoustic tomography [J]. Photoacoustics,2015,3(1):35-43.
[19] Li WQ,Wang Z,Hao S,et al. Mitochondria-targeting polydopamine nanoparticles to deliver doxorubicin for overcoming drug resistance [J]. ACS Appl Mater Interfaces,2017,9(20):16 793-16 802.
[20] Wang S,Tian Y,Tian W,et al. Selectively sensitizing malignant cells to photothermal therapy using a CD44-targetingheat shock protein 72 depletion nanosystem [J]. ACS Nano,2016,10(9):8578-8590. |
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