CN104274841A - 肿瘤血管栓塞剂以及金纳米粒子的用途 - Google Patents
肿瘤血管栓塞剂以及金纳米粒子的用途 Download PDFInfo
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Abstract
本发明提供一种肿瘤血管栓塞剂，包括：未经修饰的金纳米粒子；以及药学上可接受的介质。本发明另提供金纳米粒子在制备肿瘤血管栓塞剂的用途。
Description
技术领域
本发明涉及一种肿瘤血管栓塞剂，且特别是涉及一种纳米粒子肿瘤血管栓塞剂。
背景技术
头、颈及中枢神经系统血管肿瘤栓塞术已经成为在手术治疗外附加的一种重要肿瘤治疗方法。这种栓塞术可以减少病发及死亡率，同时能协助移除部份肿瘤。在不能进行手术治疗的肿瘤中，栓塞术可能会被用以作为主要的治疗方式。阻塞通常通过血管运输的方式进行，但亦可能会直接把栓塞物穿刺注射至肿瘤内。血管运输的方式通常是通过微导管侵入性地穿刺进动脉(例如，鼠蹊部的股动脉、颈动脉等)后引至肿瘤位置注射栓塞物以阻塞肿瘤的血液供应。这种栓塞物可为永久或暂时性，例如，液体(乙醇、丙烯酸、Onyx)或粒子(聚乙烯醇、Gelfoam)。
金纳米粒子目前已应用于多种纳米科技如生物感测、生物影像、以及纳米级治疗。在健康、诊断、以及对抗恶性疾病如癌症等生医领域中，金纳米粒子扮演重要的角色。金纳米粒子具有小尺寸以及在肿瘤部位渗透及停留作用增强等性质，可选择性地凝聚于癌组织中，因此适合作为药物传输载体或放射治疗增强剂。
目前仍需一种新的血管栓塞剂，其对肿瘤具有专一性并阻断肿瘤血管以达到抑制肿瘤生长，且可达到即时监测的效果。
发明内容
本发明提供一种肿瘤血管栓塞剂，其包括：未经修饰的金纳米粒子；以及药学上可接受的介质。
本发明另提供一种金纳米粒子的用途，其用于制备肿瘤血管栓塞剂，其中前述肿瘤血管栓塞剂用于给予至生物体内，以累积于前述生物体中的肿瘤处并栓塞前述肿瘤的血管。
附图说明
图1为将金纳米粒子以动脉注射进小鼠体内后，金纳米粒子累积并栓塞于肿瘤血管的X光图(曝光时间为100毫秒)，圆圈处为肿瘤的范围。
实施方式
以下说明本发明实施例的制作与使用。然而，可轻易了解本发明实施例提供许多合适的发明概念而可实施于广泛的各种特定背景。所揭示的特定实施例仅仅用于说明以特定方法制作及使用本发明，并非用以局限本发明的范围。
本发明主要是将未经修饰的金纳米粒子作为肿瘤血管栓塞剂注射至生物体内的肿瘤的血管中，并且以X光源照射上述生物体，使高吸收对比的金纳米粒子累积并栓塞于肿瘤血管，再利用此金纳米粒子的X光显影来观察肿瘤的情形。
上述的X光源可包括同步辐射X光源、医用X光源、或实验用X光源。X光源的波长约介于3.09×10-1-6.19×10-5nm，其能量约介于4keV-20MeV之间，可克服光子在生物体内穿透性不足的问题，得以有效激发给予至生物体内的纳米粒子。此外，由于X光源剂量足够，其照射上述生物体的时间可小于约60分钟，优选小于约5分钟，且上述X光源照射该生物体的可穿透的有效深度约为表面至组织深层30cm。由于本发明所采用的X光源在活体组织中具有穿透性，因此可通过本发明的X光显影技术即时监测活体组织内的肿瘤细胞，毋须根据传统医学影像的处理方式自活体采样切片。
本发明适用于阻断生物体内的肿瘤的血管。在一实施例中，生物体包括：哺乳类、鸟类、两栖类、爬虫类、鱼类、昆虫类、或其他合宜的多细胞动物。
在一些实施例中，上述肿瘤的种类可包括但不限于，上皮细胞肿瘤、脑部肿瘤、黑色素肿瘤、淋巴肿瘤、浆细胞瘤、肉瘤、神经胶质瘤、以及胸腺瘤；或位于口腔、食道、消化系统、呼吸系统、骨骼、关节、软组织、皮肤、乳房、生殖系统、泌尿系统、眼与眼眶、脑部与其他神经系统、内分泌系统、淋巴、或骨髓等的肿瘤。
在一实施例中，将未经修饰的金纳米粒子给予生物体内肿瘤的方法可包括，但不限于：静脉注射、动脉注射、动脉注射、淋巴注射、或局部器官注射。在一实施例中，上述纳米粒子系注射至肿瘤上游动脉中。
在一些实施例中，金纳米粒子是未经修饰的。在一实施例中，本发明所使用的金纳米粒子是以同步辐射方法生长的，其包括提供含有金离子的前驱物溶液，例如金氯酸(HAuCl4·3H2O)溶液，并将此前驱物溶液的pH值调整至碱性以避免凝聚以及尺寸不均的现象，约pH8-11左右，再利用同步辐射X射线照射此前驱物溶液(例如：BL01A储存环中4-30keV的X射线)，以将前驱物转化为金纳米粒子，其中金纳米粒子的尺寸可根据照射时间调整，照射时间越长可得尺寸较小的金纳米粒子。在一些实施例中，金纳米粒子是介于1nm-100μm之间，优选为1-50nm之间，相对较为惰性且大致上无毒，对生物体是无害的。
在一些实施例中.金纳米粒子可与药学上可接受的介质结合，例如可包括溶剂、分散液、或等渗剂(isotonic agent)等。在一些实施例中，药学上可接受的介质可包括，水、生理食盐水、糖、胶体、多孔基质、防腐剂等，或前述的组合。在一些实施例中，药学上可接受的介质为水。在一实施例中，金纳米粒子的浓度可介于1-1000mg/ml，优选为1-300mg/ml之间，例如约190mg/ml，以及其注射剂量介于0.0001-100g/kg，优选为0.0001-2g/kg，例如约0.19g/kg。
实施例
活体内金纳米粒子累积于肿瘤血管的X光影像
本实验所使用的小鼠皆由Academia Sinica Institutional Animal Care andUtilization Committee(AS IACUC)所代为饲养的BALB/c小鼠(购自国家实验动物中心，台湾)，其饲养条件为：每5只小鼠饲养于一笼子中，维持环境于温度24±2℃，湿度40％–70％下，每12小时日夜交替一次。
4-5周的小鼠以10μl的Zoletil50(50mg/kg；Virbac Laboratories,Carros,France)于肌肉注射麻醉，将PE-08导管穿刺于小鼠(体重约～20-25g)颈动脉。接着以上述PE-08导管(PE-08catheters，BB31695,Scientific Commodities,Inc.,I.D.:0.2mm,O.D.:0.36mm)将上述含有纳米金的显影剂取1000μl,50mM从颈动脉(femoral artery)注入小鼠体内晚期肿瘤(late-stage tumor，16天)，其中各组显影剂注入的速度为1μl/s。在显影过程中，小鼠皆维持在被含有1％isoflurene(麻醉气体)的氧气(1％isoflurene in oxygen)麻醉的情况下。影像为自颈动脉注射进入小鼠体内5分钟后的X光影像、其曝光时间为100毫秒，同步辐射X光源的波长约介于3.09×10-1-4.13×10-2nm，其能量约介于4keV-30keV之间，剂量小于约100Gy。结果如图1，其显示小鼠体内肿瘤血管的X光影像，金纳米粒子累积并栓塞肿瘤血管。
虽然本发明已以较佳实施例揭露如上，然其并非用以限定本发明，任何所属技术领域中具有通常知识者，在不脱离本发明的精神和范围内，当可作更动、替代与润饰。举例来说，任何所属技术领域中具有通常知识者可轻易理解此处所述的许多特征、功能、制程及材料可在本发明的范围内作更动。
Claims (13)
1.一种肿瘤血管栓塞剂，包括：
未经修饰的金纳米粒子；以及
药学上可接受的介质。
2.如权利要求1所述的肿瘤血管栓塞剂，其中该肿瘤血管栓塞剂注射进生物体的肿瘤动脉中。
3.如权利要求2所述的肿瘤血管栓塞剂，其中该生物体包括：哺乳类、鸟类、两栖类、爬虫类、鱼类、昆虫类、或其他合宜的多细胞动物。
4.如权利要求1所述的肿瘤血管栓塞剂，其中该肿瘤包括上皮细胞肿瘤、脑部肿瘤、黑色素肿瘤、淋巴肿瘤、浆细胞瘤、肉瘤、神经胶质瘤、胸腺瘤，或位于口腔、食道、消化系统、呼吸系统、骨骼、关节、软组织、皮肤、乳房、生殖系统、泌尿系统、眼与眼眶、脑部与其他神经系统、内分泌系统、淋巴、以及骨髓的肿瘤。
5.如权利要求1所述的肿瘤血管栓塞剂，其中该纳米粒子的直径介于1nm-100μm。
6.如权利要求1所述的肿瘤血管栓塞剂，其中该药学上可接受的介质包括溶剂、分散液、或等渗剂。
7.一种金纳米粒子的用途，其用于制备肿瘤血管栓塞剂，其中该肿瘤血管栓塞剂用于给予至生物体内，以累积于该生物体中的肿瘤处并栓塞该肿瘤的血管。
8.如权利要求7所述金纳米粒子的用途，其中更包括以X光源照射该生物体的该肿瘤处，以即时监测该肿瘤栓塞剂于该生物体的该肿瘤处的情形。
9.如权利要求8所述的金纳米粒子的用途，其中该X光源包括同步辐射X光源、医用X光源、或实验用X光源。
10.如权利要求8所述的金纳米粒子的用途，其中该X光源的剂量小于约100Gy。
11.如权利要求8所述的金纳米粒子的用途，其中该X光源的剂量介于约1-30Gy之间。
12.如权利要求8所述的金纳米粒子的用途，其中该X光源照射该生物体的时间约小于60分钟。
13.如权利要求8所述的金纳米粒子的用途，其中该X光源照射该生物体的时间约小于5分钟。
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| TW102123932 | 2013-07-04 | ||
| TW102123932A TWI461203B (zh) | 2013-07-04 | 2013-07-04 | 腫瘤血管栓塞劑以及金奈米粒子之用途 |
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| CN108472373A (zh) * | 2015-12-18 | 2018-08-31 | 医用装置国际株式会社 | 生物降解性肿瘤密封剂 |
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| US5776175A (en) * | 1995-09-29 | 1998-07-07 | Esc Medical Systems Ltd. | Method and apparatus for treatment of cancer using pulsed electromagnetic radiation |
| WO2000006244A2 (en) * | 1998-07-30 | 2000-02-10 | Hainfeld James F | Loading metal particles into cell membrane vesicles and metal particle use for imaging and therapy |
| EP2242539B1 (en) * | 2008-01-16 | 2015-04-01 | Nanospectra Biosciences, Inc. | Nanoparticles for focused hyperthermia to increase efficacy of radiation therapy |
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| Title |
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| GANESHCHANDRA SONAVANE 等: "Biodistribution of colloidal gold nanoparticles after intravenous administration: Effect of particle size", 《COLLOIDS AND SURFACES B: BIOINTERFACES》 * |
| JAMES F HAINFELD 等: "The use of gold nanoparticles to enhance radiotherapy in mice", 《PHYSICS IN MEDICINE AND BIOLOGY》 * |
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| CN108472373A (zh) * | 2015-12-18 | 2018-08-31 | 医用装置国际株式会社 | 生物降解性肿瘤密封剂 |
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| US20150011818A1 (en) | 2015-01-08 |
| TW201501715A (zh) | 2015-01-16 |
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