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首页> 外文期刊>Biomaterials Science >Biocompatibility, biodistribution and efficacy of magnetic nanohydrogels in inhibiting growth of tumors in experimental mice models
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Biocompatibility, biodistribution and efficacy of magnetic nanohydrogels in inhibiting growth of tumors in experimental mice models

机译：磁性纳米水凝胶在实验小鼠模型中的生物相容性，生物分布和抑制肿瘤生长的功效

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摘要

We report in vivo evaluation of a thermo-responsive poly(N-isopropylacrylamide)-chitosan based magnetic nanohydrogel (MNHG) incorporated with Fe_3O_4 nanoparticles (NPs) in mice models with expandible scope for use in localized delivery of chemotherapeutics. Biocompatibility and biodistribution of the MNHG are studied in normal Swiss mice while efficacy in tumor growth inhibition is studied in a subcutaneous fibrosarcoma tumor. The ex vivo time-dependent pattern of accumulated MNHG into vital organs; lung, liver, spleen, kidney and brain collected at 1 h, 48 h, 7 d and 14 d post intravenous administration are investigated using both a vibrating sample magnetometer (VSM) and inductively coupled plasma-atomic emission spectroscopy (ICP-AES) method. The doses of MNHG (dose I ～ 650 and dose II ～ 325 μg g~(-1) body wt) used in the study are determined based on induced thermal activation of MNHG under an AC magnetic field (AMF). Fibrosarcoma tumor bearing mice are subjected to hyperthermia with a field of 325 Oe and 265 kHz for 30 min following intratumoral administration of dose I. Tumor size measured at an interval of 72 h for a period of 2 weeks reveals that the NPs mediated therapy decelerated the growth of the transplanted tumor by about three-fold (size, 1545 ± 720 mm~3) as compared to the exponential growth of the tumor (size, 4510 ± 735 mm~3) in control mice. These results suggest the feasibility of using poly(NIPAAm)-chitosan hydrogels loaded with NPs for combined thermo-chemotherapy where the efficacy may further be improved by temperature dependent release of the drugs from the magneto hydrogels.
机译：我们报告在体内模型的可扩展范围用于化疗药物的小鼠模型中结合了Fe_3O_4纳米粒子（NPs）的热响应性聚（N-异丙基丙烯酰胺）-壳聚糖基磁性纳米水凝胶（MNHG）的体内评估。在正常的瑞士小鼠中研究了MNHG的生物相容性和生物分布，而在皮下纤维肉瘤肿瘤中研究了抑制肿瘤生长的功效。 MNHG积累到重要器官的离体时间依赖性模式;使用振动样品磁力计（VSM）和电感耦合等离子体原子发射光谱法（ICP-AES）研究了静脉给药后1小时，48小时，7天和14天收集的肺，肝，脾，肾和脑。研究中使用的MNHG剂量（剂量I〜650和剂量II〜325μgg〜（-1）体重）是基于在交流磁场（AMF）下诱导的MNHG热活化而确定的。瘤内施用剂量I后，对患有纤维肉瘤肿瘤的小鼠进行325 Oe和265 kHz电场的热疗30分钟。在72小时间隔内测量的肿瘤大小持续2周，这表明NPs介导的治疗使小鼠的NP减速。与对照小鼠中肿瘤的指数生长（4510±735 mm〜3）相比，移植肿瘤的生长大约三倍（尺寸为1545±720 mm〜3）。这些结果表明，使用载有NP的聚（NIPAAm）-壳聚糖水凝胶进行联合热化学疗法的可行性，其中通过从磁水凝胶中释放依赖温度的药物可以进一步提高疗效。

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