磁性、声学和光学三响应性微泡，用于磁性高温和波托托热组合癌症治疗
Summary
这里介绍了一个协议，通过自组装，协同磁性，声学和光学响应性在一个纳米治疗平台的磁性高温和光热组合癌症治疗制造氧化铁纳米粒子壳微泡（NSMs）。
Abstract
抗癌剂的精确输送，旨在有针对性和深度渗透的分娩，以及在肿瘤部位的对照释放，已受到挑战。在这里，我们通过自组装、协同磁性、声学和光学响应性，在一个纳米治疗平台上制造氧化铁纳米粒子壳化微泡 （NSM）。氧化铁纳米粒子既可用作磁性剂，又可用作光热剂。静脉注射后，NSM可磁性引导至肿瘤位点。超声波触发氧化铁纳米粒子的释放，由于微泡的腔作用，促进纳米粒子深入肿瘤。此后，磁性高温和光热疗法可以在肿瘤上进行合并癌症治疗，这是治疗肿瘤异质性对癌症的抵抗力的一种解决方案。在本协议中，对NSM进行了合成和定性，包括结构、化学、磁性和声学特性。此外，还利用体外细胞培养物对热疗法的抗癌疗效进行了调查。拟议的分娩策略和联合治疗在癌症治疗方面有很大的希望，以提高分娩和抗癌的疗效。
Introduction
癌症是最致命的疾病之一，每年在全世界造成数百万人死亡和巨大的经济损失。在诊所，传统的抗癌疗法，如手术切除，放疗和化疗仍然不能提供令人满意的治疗效果2。这些疗法的局限性是高毒副作用，高复发率和高转移率3。例如，化疗是遭受化疗药物的低交付效率正是肿瘤部位4。药物无法深入肿瘤组织跨越生物屏障，包括细胞外基质和高肿瘤间质液压，也是导致疗效低的原因。此外，肿瘤耐药性通常发生在接受单次化疗治疗的患者中。因此，发生肿瘤热消融的技术，如光热疗法（PTT）和磁性高温治疗（MHT），已经显示出了降低肿瘤抵抗力的可喜结果，并已在临床试验7，8，9中出现。
PTT通过光热转换剂在激光能量照射下的作用触发癌细胞的热消融。产生的高温（高于50°C）诱导完整的细胞坏死10。最近，氧化铁纳米粒子（IONPs）被证明是一种光热转换剂，可以通过近红外（NIR）光11激活。 尽管近红外区域的摩尔吸收系数较低，但IONP是低温（43°C）光热疗法的候选者，这是一种经过改良的疗法，旨在减少热暴露对正常组织造成的损害，并启动肿瘤转移的抗肿瘤免疫力。PTT的局限性之一是激光的低穿透深度。对于深座肿瘤，交替磁场（AFM）诱导加热的氧化铁纳米粒子，也被称为磁性高温，是PTT13，14的替代疗法。MHT的主要优点是磁场15的高渗透率。然而，需要相对较高的IONP浓度仍然是其临床应用的主要劣势。由于循环、积累和渗透等一系列障碍，纳米医学（或纳米粒子）对动物实体肿瘤的输送效率一直为1-10%。因此，具有高组织渗透能力的受控和有针对性的IONP输送策略对癌症治疗非常感兴趣。
超声介质纳米粒子的输送已经显示出它的能力，以促进纳米粒子深入肿瘤组织，由于现象称为微泡腔18，19。在本研究中，我们通过在一个纳米治疗平台中自组装、协同磁性、声学和光学响应性来制造离子体壳化微气泡（NSM）。NSM 包含空气核心和氧化铁纳米粒子壳，直径约为 5.4 μm。NSM 可以磁引导到肿瘤位点。然后，IONP 的释放由超声波触发，并伴有微泡空腔和微流。从微流获得的势头有助于离子体渗透到肿瘤组织中。PTT 和 MHT 可以通过 NIR 激光照射或 AFM 应用或两者的组合实现。
Protocol
Representative Results
Discussion
在这里，我们提出了一个协议，通过自组装，协同磁性，声学和光学响应性在一个纳米治疗平台制造氧化铁纳米粒子壳微泡（NSM）。IONP 被密集地包装在空气核心周围，形成磁壳，磁壳可以由外部磁场控制以进行瞄准。一旦交付，通过超声波触发器可以实现离子点的释放。释放的 IONP 可以通过 PTT 和 MHT 的 NIR 光和 AFM 激活，也可以同时激活两者的组合。
在整个协议中，NSM的合?…
Disclosures
The authors have nothing to disclose.
Acknowledgements
这项工作得到了中国国家自然科学基金委员会（81601608）和NUPTSF（NY216024）的支持。
Materials
| 808 nm laser power | Changchun New Industries Optoelectronics Tech | MDL-F-808-5W-18017023 | |
| Calcein-AM | Thermo Fisher SCIENTIFIC | C3099 | |
| Fetal bovine serum | Invitrogen | 16000-044 | |
| Fluorescence Microscope | Olympus | IX71 | |
| Function generator | Keysight | 33500B series | 20 MHz, 2 channels with arbitrary waveform generation capability |
| Gelatin gel | Sigma | 9000-70-8 | |
| Heating machine | Shuangping | SPG-06- II | |
| Homemade focused transducer | Frequency=855, R-X=36.2W+5.8W, |Z|-θ=37W+8° | ||
| Homogenizer | SCILOGEX | D-160 | 8000-30000 rpm |
| Hydrophone | T&C | NH1000 | |
| ICR male mice | OG Pharmaceutical. Co. Ltd | 8-week-old | |
| Inductively coupled plasma optical emission spectrometry | PerkinElmer | ||
| Infrared thermal imaging camera. | FLIR | E50 | |
| Iron(II,III) oxide | Alfa Aesar | 1317-61-9 | 50-100nm APS Powder |
| Laser power meter | Changchun New Industries Optoelectronics Tech | ||
| Oscilloscope | Keysight | DSOX3054T | Bandwidth 500 MHz, Sampling Rate 5 GS/S, 4 channels |
| RF Power Amplifier | T&C | AG1020 | The signal source can also be connected to an external signal source. The gain can be adjusted from 0 to 100%. It has multiple functions such as frequency sweep, pulse, and triangle. |
| Roswell Park Memorial Institute-1640 | KeyGEN BioTECH | KGM31800 | |
| Sodium dodecyl sulfate | Sigma | 151-21-3 | |
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