纳米材料介导的骨靶向光热治疗转移性骨肿瘤的研究

发布时间：2018-06-02 18:41

本文选题：骨靶向材料 + 植酸　；参考：《第二军医大学》2017年硕士论文

【摘要】：一、研究目的转移性骨肿瘤是癌症高发且致命的并发症,但目前缺少有效的临床治疗,常见的治疗方法为手术治疗、放射学治疗、化学药物治疗等,但几种疗法都存在一定缺陷。手术治疗创伤大,易复发;放疗有引起组织细胞恶变的风险;化疗对机体毒副作用较大,且肿瘤病人身体虚弱,常难以承受化学治疗的持续进行。因此寻找毒性低、副作用小、效果好的治疗转移性骨肿瘤的新思路尤为重要。光热治疗(Photo-thermal Therapy,PTT)是一种针对多种肿瘤的新型治疗策略,有诸多优于传统方法的优势,在肿瘤治疗领域受到广泛关注,且疗效肯定。近红外光线对生物组织穿透能力较强,可深达患处,经靶向纳米药物将光能转换成热能,准确提高肿瘤部位的温度,可在减小正常组织损伤情况下,利用局部过热引起的热杀伤作用有效治疗肿瘤。所以,光热治疗作为转移性骨肿瘤治疗的一种新方法,具有良好的临床前景。开发可介导骨靶向的高效纳米光热材料是将光热治疗成功应用于转移性骨肿瘤治疗的关键。已经证明,光热纳米材料在其他种类的转移性肿瘤的光热治疗中效果明显、确切,但应用光热治疗转移性骨肿瘤的研究目前仍较少。现有光热材料的骨靶向性弱,光热治疗效果差,生物相容性差,存在慢性毒性作用,都限制了光热治疗在转移性骨肿瘤中的应用。所以设计出适用于转移性骨肿瘤光热治疗的新型纳米材料,使其具有骨靶向能力强,光热性能强,生物安全性好等性能与特点,是转移骨肿瘤光热治疗的重要基础。本研究拟以植酸为骨靶向材料,合成一种可介导骨靶向的高效的植酸-铂纳米光热材料。植酸螯合钙离子的能力强,有靶向骨肿瘤潜能,且植酸有极低毒性及抑癌活性,能一定程度上抑制癌细胞的生长。铂纳米颗粒则具有高效的光热转换效率,且具有生物安全性。合成的植酸-铂纳米光热材料尺寸分布在5 nm以内,能够快速通过肾脏清除,减少了纳米颗粒在体内潴留。本课题通过研究这种新型植酸-铂纳米材料的合成、骨靶向能力、光热性能、生物安全性等多方面特征,明确其对转移性骨肿瘤光热治疗的效果,为开拓转移性骨肿瘤的光热治疗新技术提供新的思路。二、研究方法(1)植酸-铂纳米颗粒的制备及表征:使用氯铂酸、柠檬酸三钠和植酸合成植酸为模版合成的铂纳米颗粒,建立其制备技术。通过透射电子显微镜来观察植酸-铂纳米材料的大小及形态;(2)植酸-铂纳米颗粒的螯合能力和光热效能检测:通过光热效应实验观察植酸-铂纳米颗粒的光热效果。应用人工骨(羟基磷灰石)吸附实验观察植酸-铂纳米颗粒的螯合钙离子能力。(3)植酸-铂纳米颗粒的细胞毒性检测:应用MTT法观察该纳米颗粒的细胞毒性。(4)植酸-铂纳米颗粒的骨肿瘤治疗能力检测:建立肺癌胫骨转移性骨肿瘤裸鼠模型,用近红外光照射胫骨肿瘤进行光热治疗,观察其对骨肿瘤靶向性、光热性以及骨肿瘤细胞的杀伤效应。三、研究结果(1)成功建立了以植酸为模版的铂纳米颗粒合成技术。发现了该植酸-铂纳米颗粒物理表征稳定,颗粒大小在2-3nm范围内,形态相似性好。(2)该植酸-铂纳米颗粒在808nm处有良好的吸光效果,热效应良好有效。在体外吸附的实验中,对比两块人工骨我们可以发现实验组的吸附程度高、吸附能力强。(3)植酸-铂颗粒的生物相容性具有浓度依赖关系。(4)该植酸-铂纳米颗粒对肺癌胫骨转移性骨肿瘤裸鼠模型具有良好的体内骨肿瘤靶向能力,光热治疗效果好,肿瘤抑制作用明确,生物安全性良好,具有对转移性骨肿瘤的治疗作用。四、结论本研究成功制备了一种以天然植物成分无害成分植酸为模版合成的新型超小铂纳米材料,该材料具有尺寸超小,稳定分散存在,体内外均具有良好的骨靶向性能,无明显毒副作用,生物相容性好,光热治疗转移性骨肿瘤效果明确的优势。这种新型植酸-铂纳米材料为转移性骨肿瘤的光热治疗提供了新的视角。
[Abstract]:First, metastatic bone tumor is a high and fatal complication of cancer, but there is a lack of effective clinical treatment. The common treatment methods are surgical treatment, radiology treatment, chemical therapy and so on. However, there are certain defects in several treatments. Surgical treatment is very traumatic and easy to relapse; radiotherapy has the risk of causing malignant transformation of tissue cells. The treatment of patients with toxic side effects, and the cancer patients are weak, often difficult to sustain the continuous chemical treatment. Therefore, it is particularly important to find new ideas for the treatment of metastatic bone tumors with low toxicity, small side effects and good effect. Photo-thermal Therapy (PTT) is a new treatment strategy for many kinds of tumors and has many advantages. The advantages of traditional methods are widely concerned in the field of cancer treatment, and the effect is positive. Near infrared ray has a strong penetration ability to biological tissue. It can reach the affected part and transform the light energy into heat energy by targeting nano drugs. It can improve the temperature of the tumor site accurately. It can be used to kill the heat caused by local overheating under the condition of Jian Xiaozheng normal tissue damage. The effect of injury is effective in the treatment of tumors. Therefore, photothermal therapy is a new method for the treatment of metastatic bone tumors. It has a good clinical prospect. It is the key to successfully apply photothermal therapy to the treatment of metastatic bone tumors. It has been proved that photothermal nanomaterials are transferred to other kinds of metastasis. The effect of photothermal therapy on sexual tumor is obvious, accurate, but the study of photothermal treatment for metastatic bone tumor is still less. The present light heat material has weak bone targeting, poor photothermal treatment effect, poor biocompatibility and chronic toxicity, which restricts the application of photothermal therapy in metastatic bone tumor. A new type of nano material for photothermal treatment of graft bone tumor, which has strong bone targeting ability, strong photothermal performance and good biological safety, is an important basis for the photothermal treatment of metastatic bone tumors. This study is to use phytic acid as a bone targeting material to synthesize a highly efficient phytate platinum nano photothermal material which can mediate bone targeting. Calcium ions have strong ability to target bone tumor potential, and phytic acid has extremely low toxicity and tumor suppressor activity. It can inhibit the growth of cancer cells to a certain extent. Platinum nanoparticles have high efficiency of photothermal conversion and biological safety. The size of the synthesized phytic acid platinum nanoscale materials is within 5 nm, which can quickly pass through the kidney. In this study, the effect of photothermal treatment on metastatic bone tumor was clearly defined by studying the synthesis of this new type of phytic acid - Platinum nanomaterials, bone targeting ability, photothermal performance and biosafety, and providing new ideas for the development of new techniques for the development of photothermal treatment for metastatic bone tumors. Two Research methods (1) preparation and characterization of phytic acid platinum nanoparticles: platinum nanoparticles were synthesized using chlorinated platinum acid, sodium citrate three and phytic acid as template. The size and morphology of phytic acid platinum nanomaterials were observed by transmission electron microscopy. (2) the chelating ability and photothermal efficacy of phytic acid platinum nanoparticles. Test: the photothermal effect of phytic acid platinum nanoparticles was observed by photothermal effect. Artificial bone (hydroxyapatite) adsorption experiment was used to observe the chelating calcium ion ability of phytic acid platinum nanoparticles. (3) cytotoxicity test of phytic acid platinum nanoparticles: MTT method was used to observe the cytotoxicity of the nanoparticles. (4) the bone swelling of phytic platinum nanoparticles. Tumor treatment ability test: to establish nude mice model of bone tumor of tibial metastatic bone of lung cancer, irradiate tibial tumor with near infrared light to perform photothermal treatment, observe its targeting, photothermal and bone tumor cell killing effect. Three, the result of study (1) successfully established the synthesis technology of platinum nanoparticles with phytic acid as template. The physical characterization of the acid platinum nanoparticles is stable, the size of the particles is within the range of 2-3nm, and the morphological similarity is good. (2) the phytic acid platinum nanoparticles have good absorption effect at 808nm, and the thermal effect is good and effective. In the experiment of adsorption in vitro, we can compare two artificial bones with high adsorption and strong adsorption capacity. (3) phytic acid platinum. The biocompatibility of the particles has a concentration dependence. (4) the phytate platinum nanoparticles have good targeting ability to the bone tumor in the nude mice of the tibial metastatic bone tumor of lung cancer, the effect of photothermal therapy is good, the tumor suppressor is clear, the biological safety is good, and it has the therapeutic effect on the metastatic bone tumor. Four. Conclusion this study is a conclusion. A new type of super small platinum Nanomaterials Synthesized from natural plant component phytic acid as template was prepared. The material has the advantages of super small size, stable dispersion, good bone targeting in vivo and in vivo, no obvious side effects, good biocompatibility, and clear effect of photothermal treatment for metastatic bone tumor. Phytic acid platinum nanoparticles provide a new perspective for photothermal therapy of metastatic bone tumors.
【学位授予单位】：第二军医大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R738

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