创新背景

在过去30年里，癌症早期发现和治疗方面的进展帮助降低了30%以上的总死亡率。然而，胰腺癌仍然很难治疗。只有九分之一的人在确诊后能活过五年，部分原因是这种癌症受到生物因素的保护，帮助它抵抗治疗。

创新过程

为了扭转这一趋势，加州大学洛杉矶分校(UCLA)的研究人员开发了一种技术，通过纳米级颗粒装载伊立替康（一种被批准为胰腺癌药物方案一部分的化疗药物）和3M-052（一种可以增强免疫活性并帮助克服肿瘤耐药性的研究药物）对胰腺肿瘤进行联合治疗。

研究人员的双载纳米载体在缩小肿瘤和防止小鼠癌症转移方面比没有纳米载体的伊立替康或独立提供两种药物的纳米载体更有效。联合疗法还吸引了更多的抗癌免疫细胞到肿瘤部位，并使血液中的药物水平维持了更长的时间。没有证据表明有有害的副作用。

纳米载体的中空玻璃气泡（白色，左）填充有伊立替康（绿色），并被含有免疫嘘声药物3M-052（右侧特写图像中的橙色颗粒）的脂质层（蓝色）覆盖。

除了阻止癌细胞生长，伊立替康还向免疫系统的树突细胞发送危险信号；它们又会调动杀伤T细胞，杀伤T细胞到达肿瘤部位并摧毁癌细胞。但由于胰腺癌患者的树突状细胞通常功能受损，3M-052提供了额外的帮助，帮助它们更好地聚集癌症部位和附近淋巴结的杀伤T细胞。

大多数纳米载体是由脂肪物质组成的脂质分子层组成的，类似于细胞膜，有可以包装药物的空间。在这种新装置中，双层脂质包裹着一个由二氧化硅制成的核心玻璃气泡，其中空的内部可以被伊立替康填充。研究人员发现，3-052分子的脂肪尾巴可以用来将第二种药物直接整合到这些外层脂质层中。

这种载体的结构设计非常小，需要1000个这样的载体才能跨越头发丝的宽度。当这种载体进入保护胰腺癌的强大的绳状屏障并到达肿瘤部位时，它有助于防止药物泄漏和毒性。与其他药物载体相比，玻璃微珠提供了额外的防止泄漏的保护，使载体能够向肿瘤部位输送更多的伊立替康。

该团队将进行进一步的临床前实验，以测试它们在大型动物模型中的治疗效果，并确定大规模制造二氧化硅纳米载体的质量控制。

创新关键点

研究人员发明新“玻璃气泡”装置装载伊立替康和3M-052对胰腺肿瘤进行联合治疗。

创新价值

研究团队表明，在胰腺癌小鼠模型中，同时递送的组合物比各部分加起来的效果要好。这种新方法可有效治疗胰腺癌。

Innovative development of "glass bubble" nanocarriers can improve the efficacy of pancreatic cancer combination therapy

To reverse this trend, researchers at the University of California, Los Angeles (UCLA) developed a technique to treat pancreatic tumors by loading nano-sized particles with a combination of irinotecan, a chemotherapy drug approved as part of the pancreatic cancer drug regimen, and 3M-052, an investigational drug that can boost immune activity and help overcome tumor resistance.
The researchers' double-loaded nanocarriers were more effective at shrinking tumors and preventing cancer metastasis in mice than irinotecan without the nanocarriers or nanocarriers that delivered both drugs independently. The combination therapy also attracted more cancer-fighting immune cells to the tumor site and kept drug levels in the blood for a longer period of time. There is no evidence of harmful side effects.

In addition to stopping cancer cell growth, irinotecan sends a danger signal to the immune system's dendritic cells; They in turn mobilize killer T cells, which travel to the tumor site and destroy the cancer cells. But because dendritic cells in pancreatic cancer patients are often functionally impaired, 3M-052 provides additional help by helping them better gather killer T cells at the cancer site and in nearby lymph nodes.

Most nanocarriers are composed of layers of lipid molecules made of fatty material, similar to cell membranes, with room to pack drugs. In the new device, a double layer of lipid surrounds a core glass bubble made of silica, the empty interior of which can be filled with irinotecan. The researchers found that the fatty tail of the 3-052 molecule could be used to integrate a second drug directly into these outer lipid layers.

The structure of the carrier is so small that it would take 1,000 of them to span the width of a human hair. When the carrier enters the powerful rope barrier that protects pancreatic cancer and reaches the tumor site, it helps prevent drug leakage and toxicity. Glass microbeads provide additional protection against leakage compared to other drug carriers, allowing the carrier to deliver more irinotecan to the tumor site.

The team will conduct further preclinical experiments to test their therapeutic effect in large animal models and to determine quality control for the large-scale manufacture of silica nanocarriers.