MIT一项新研究通过研究小鼠指出，T细胞可作为“特洛伊木马”而将载有药物的纳米颗粒偷运至淋巴瘤中，这将改善化疗的功效。这些结果表明，T细胞可增强向淋巴瘤及向其他类型癌症的难以接近的肿瘤的药物输送。尽管化疗药物是强力的癌肿杀手，但它们会无法到达偏远位置的肿瘤，因此常常需要给予产生毒性的高剂量才能凑效。淋巴瘤在药物输送上尤其面临严峻的挑战。这种癌症始于白细胞，它常常会扩散至身体的其他器官，其中包括淋巴结，而后者已知会给肿瘤提供躲避循环系统中药物的避风港。Bonnie Huang和同事在此证明，健康的T细胞可提供一个天然的肿瘤追踪系统，因为它们能迁移至其癌性对等细胞所能进入的相同组织。应用一个小鼠的凶险型淋巴瘤模型，研究人员从血液中分离出了健康的T细胞，并在专门的培养过程中让它们生长以保留能指导T细胞接近淋巴组织的受体。接着他们将载有一种常见化疗药物的纳米颗粒附着在这些T细胞的表面，并将这些T细胞重新注射到小鼠体内。该饰有纳米颗粒T细胞的减少肿瘤及延长存活时间的效果要强于纳米颗粒包裹的药物或游离药物的效果。这些结果表明，T细胞帮助将这些包有纳米颗粒的药物输送至散布的肿瘤中，其中包括那些在淋巴结中的肿瘤。由Jeffrey Hubbell撰写的一则相关的《焦点》文章对这种T细胞药物输送系统以及其他基于细胞的药物输送平台的设计和临床潜力进行了更为详细的讨论。
文字说明: 带药细胞以难以接近的肿瘤和其它组织作为标靶。Huang和其同事用基于脂质的能与T细胞表面结合的纳米颗粒(它们被一同称作“带药细胞”)将隐藏在淋巴结中的淋巴瘤作为标靶;淋巴结是一种难以接近的解剖位置;该纳米颗粒含有抗癌药SN-38。
原文链接：Active targeting of chemotherapy to disseminated tumors using nanoparticle-carrying T cells
原文摘要：Tumor cells disseminate into compartments that are poorly accessible from circulation, which necessitates high doses of systemic chemotherapy. However, the effectiveness of many drugs, such as the potent topoisomerase I poison SN-38, is hampered by poor pharmacokinetics. To deliver SN-38 to lymphoma tumors in vivo, we took advantage of the fact that healthy lymphocytes can be programmed to phenocopy the biodistribution of the tumor cells. In a murine model of disseminated lymphoma, we expanded autologous polyclonal T cells ex vivo under conditions that retained homing receptors mirroring lymphoma cells, and functionalized these T cells to carry SN-38–loaded nanocapsules on their surfaces. Nanocapsule-functionalized T cells were resistant to SN-38 but mediated efficient killing of lymphoma cells in vitro. Upon adoptive transfer into tumor-bearing mice, these T cells served as active vectors to deliver the chemotherapeutic into tumor-bearing lymphoid organs. Cell-mediated delivery concentrated SN-38 in lymph nodes at levels 90-fold greater than free drug systemically administered at 10-fold higher doses. The live T cell delivery approach reduced tumor burden significantly after 2 weeks of treatment and enhanced survival under conditions wher free SN-38 and SN-38–loaded nanocapsules alone were ineffective. These results suggest that tissue-homing lymphocytes can serve as specific targeting agents to deliver nanoparticles into sites difficult to access from the circulation, and thus improve the therapeutic index of chemotherapeutic drugs with unfavorable pharmacokinetics.
