本文選題：骨靶向材料 + 植酸　； 參考：《第二軍醫(yī)大學》2017年碩士論文

【摘要】：一、研究目的轉移性骨腫瘤是癌癥高發(fā)且致命的并發(fā)癥,但目前缺少有效的臨床治療,常見的治療方法為手術治療、放射學治療、化學藥物治療等,但幾種療法都存在一定缺陷。手術治療創(chuàng)傷大,易復發(fā);放療有引起組織細胞惡變的風險;化療對機體毒副作用較大,且腫瘤病人身體虛弱,常難以承受化學治療的持續(xù)進行。因此尋找毒性低、副作用小、效果好的治療轉移性骨腫瘤的新思路尤為重要。光熱治療(Photo-thermal Therapy,PTT)是一種針對多種腫瘤的新型治療策略,有諸多優(yōu)于傳統(tǒng)方法的優(yōu)勢,在腫瘤治療領域受到廣泛關注,且療效肯定。近紅外光線對生物組織穿透能力較強,可深達患處,經靶向納米藥物將光能轉換成熱能,準確提高腫瘤部位的溫度,可在減小正常組織損傷情況下,利用局部過熱引起的熱殺傷作用有效治療腫瘤。所以,光熱治療作為轉移性骨腫瘤治療的一種新方法,具有良好的臨床前景。開發(fā)可介導骨靶向的高效納米光熱材料是將光熱治療成功應用于轉移性骨腫瘤治療的關鍵。已經證明,光熱納米材料在其他種類的轉移性腫瘤的光熱治療中效果明顯、確切,但應用光熱治療轉移性骨腫瘤的研究目前仍較少�，F有光熱材料的骨靶向性弱,光熱治療效果差,生物相容性差,存在慢性毒性作用,都限制了光熱治療在轉移性骨腫瘤中的應用。所以設計出適用于轉移性骨腫瘤光熱治療的新型納米材料,使其具有骨靶向能力強,光熱性能強,生物安全性好等性能與特點,是轉移骨腫瘤光熱治療的重要基礎。本研究擬以植酸為骨靶向材料,合成一種可介導骨靶向的高效的植酸-鉑納米光熱材料。植酸螯合鈣離子的能力強,有靶向骨腫瘤潛能,且植酸有極低毒性及抑癌活性,能一定程度上抑制癌細胞的生長。鉑納米顆粒則具有高效的光熱轉換效率,且具有生物安全性。合成的植酸-鉑納米光熱材料尺寸分布在5 nm以內,能夠快速通過腎臟清除,減少了納米顆粒在體內潴留。本課題通過研究這種新型植酸-鉑納米材料的合成、骨靶向能力、光熱性能、生物安全性等多方面特征,明確其對轉移性骨腫瘤光熱治療的效果,為開拓轉移性骨腫瘤的光熱治療新技術提供新的思路。二、研究方法(1)植酸-鉑納米顆粒的制備及表征:使用氯鉑酸、檸檬酸三鈉和植酸合成植酸為模版合成的鉑納米顆粒,建立其制備技術。通過透射電子顯微鏡來觀察植酸-鉑納米材料的大小及形態(tài);(2)植酸-鉑納米顆粒的螯合能力和光熱效能檢測:通過光熱效應實驗觀察植酸-鉑納米顆粒的光熱效果。應用人工骨(羥基磷灰石)吸附實驗觀察植酸-鉑納米顆粒的螯合鈣離子能力。(3)植酸-鉑納米顆粒的細胞毒性檢測:應用MTT法觀察該納米顆粒的細胞毒性。(4)植酸-鉑納米顆粒的骨腫瘤治療能力檢測:建立肺癌脛骨轉移性骨腫瘤裸鼠模型,用近紅外光照射脛骨腫瘤進行光熱治療,觀察其對骨腫瘤靶向性、光熱性以及骨腫瘤細胞的殺傷效應。三、研究結果(1)成功建立了以植酸為模版的鉑納米顆粒合成技術。發(fā)現了該植酸-鉑納米顆粒物理表征穩(wěn)定,顆粒大小在2-3nm范圍內,形態(tài)相似性好。(2)該植酸-鉑納米顆粒在808nm處有良好的吸光效果,熱效應良好有效。在體外吸附的實驗中,對比兩塊人工骨我們可以發(fā)現實驗組的吸附程度高、吸附能力強。(3)植酸-鉑顆粒的生物相容性具有濃度依賴關系。(4)該植酸-鉑納米顆粒對肺癌脛骨轉移性骨腫瘤裸鼠模型具有良好的體內骨腫瘤靶向能力,光熱治療效果好,腫瘤抑制作用明確,生物安全性良好,具有對轉移性骨腫瘤的治療作用。四、結論本研究成功制備了一種以天然植物成分無害成分植酸為模版合成的新型超小鉑納米材料,該材料具有尺寸超小,穩(wěn)定分散存在,體內外均具有良好的骨靶向性能,無明顯毒副作用,生物相容性好,光熱治療轉移性骨腫瘤效果明確的優(yōu)勢。這種新型植酸-鉑納米材料為轉移性骨腫瘤的光熱治療提供了新的視角。
[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.
【學位授予單位】：第二軍醫(yī)大學
【學位級別】：碩士
【學位授予年份】：2017
【分類號】：R738

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