靶向三阴性乳腺癌微环境神经细胞
神经细胞又称神经元，主要分布于神经系统，还分布于肿瘤微环境，可促进癌症进展。因此，局部靶向肿瘤微环境的神经元可能带来临床获益。不过，如何局部靶向肿瘤微环境的神经元？以色列和西班牙科学家们想到了局部麻醉剂。
2021年10月8日，美国科学促进会《科学》旗下《科学进展》发表以色列理工学院、耶路撒冷希伯来大学哈达萨医学院、特拉维夫大学索拉斯基医疗中心、西班牙巴斯克自治区大学、圣地亚哥德孔波斯特拉健康研究所的研究报告，采用布比卡因纳米颗粒靶向肿瘤微环境的神经元，可显著减少三阴性乳腺癌的进展和转移。
该研究设计了装载非阿片类局部麻醉剂布比卡因的聚乙二醇化脂质纳米颗粒，可靶向乳腺癌肿瘤微环境的神经元，并抑制神经与乳腺癌之间的信号传导。
体外研究表明，100纳米颗粒非常容易从神经元体和轴突运输至初级神经元被吸收。三阴性乳腺癌细胞4T1与神经元之间的信号传导可参与刺激神经突生长的细胞因子分泌。反之，神经元通过分泌神经递质可刺激4T1的增殖、迁移和存活。布比卡因可抑制神经突生长和癌细胞信号传导，抑制癌细胞运动能力。
体内研究表明，静脉注射布比卡因纳米颗粒可抑制原位三阴性乳腺癌肿瘤微环境的神经元，抑制肿瘤的生长和转移传播。
因此，该研究结果表明，减少肿瘤微环境的神经元对于治疗癌症至关重要，故有必要进一步开展人体临床研究进行验证。
Sci Adv. 2021 Oct 8;7(41):eabj5435.
Targeting neurons in the tumor microenvironment with bupivacaine nanoparticles reduces breast cancer progression and metastases.
Kaduri M, Sela M, Kagan S, Poley M, Abumanhal-Masarweh H, Mora-Raimundo P, Ouro A, Dahan N, Hershkovitz D, Shklover J, Shainsky-Roitman J, Buganim Y, Schroeder A.
Technion-Israel Institute of Technology, Haifa, Israel; The Hebrew University Hadassah Medical School, Jerusalem, Israel; Sourasky Medical Center, Tel Aviv, Israel; University of the Basque Country, Bilbao, Spain; Health Research Institute of Santiago de Compostela, Santiago de Compostela, Spain.
Neurons within the tumor microenvironment promote cancer progression; thus, their local targeting has potential clinical benefits. We designed PEGylated lipid nanoparticles loaded with a non-opioid analgesic, bupivacaine, to target neurons within breast cancer tumors and suppress nerve-to-cancer cross-talk. In vitro, 100-nm nanoparticles were taken up readily by primary neurons, trafficking from the neuronal body and along the axons. We demonstrate that signaling between triple-negative breast cancer cells (4T1) and neurons involves secretion of cytokines stimulating neurite outgrowth. Reciprocally, neurons stimulated 4T1 proliferation, migration, and survival through secretion of neurotransmitters. Bupivacaine curbs neurite growth and signaling with cancer cells, inhibiting cancer cell viability. In vivo, bupivacaine-loaded nanoparticles intravenously administered suppressed neurons in orthotopic triple-negative breast cancer tumors, inhibiting tumor growth and metastatic dissemination. Overall, our findings suggest that reducing nerve involvement in tumors is important for treating cancer.
PMID: 34613777
DOI: 10.1126/sciadv.abj5435