In women with human epidermal growth factor 2 (HER2)-positive breast cancer, the improved control of systemic disease with new therapies has unmasked brain metastases that historically would have remained clinically silent. The efficacy of therapeutic agents against brain metastases is limited by their inability to permeate the blood-brain and blood-tumor barriers (BBB and BTB) in therapeutic amounts. Here, we investigate the potential of mucic acid-based, targeted nanoparticles designed to transcytose the BBB/BTB to deliver a small molecule drug, camptothecin (CPT), and therapeutic antibody, Herceptin, to brain metastases in mice. Treatment with BBB-targeted combination CPT/Herceptin nanoparticles significantly inhibits tumor growth compared to free CPT/Herceptin and BBB-targeted nanoparticles carrying CPT alone. Though not as efficacious, BBB-targeted nanoparticles carrying only Herceptin also elicit considerable antitumor activity. These results demonstrate the potential of the targeted nanoparticle system for the delivery of an antibody alone or in combination with other drugs across the BBB/BTB to improve the therapeutic outcome.

中文翻译：

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包含药物和抗体的组合治疗乳腺癌脑转移的纳米粒子。

在具有人类表皮生长因子2（HER2）阳性乳腺癌的女性中，通过新疗法改善对系统性疾病的控制已掩盖了脑转移瘤，而从历史上看，脑转移瘤在临床上一直保持沉默。治疗剂对抗脑转移的功效受其无法渗透治疗量的血脑屏障和血肿瘤屏障（BBB和BTB）的限制。在这里，我们研究了基于粘液酸的靶向纳米颗粒的潜力，该纳米颗粒旨在转染BBB / BTB，以向小鼠脑转移中传递小分子药物喜树碱（CPT）和治疗性抗体赫赛汀。与单独携带CPT的游离CPT / Herceptin和BBB靶向的纳米颗粒相比，以BBB靶向的组合CPT / Herceptin纳米颗粒治疗显着抑制了肿瘤的生长。虽然没有那么有效，仅携带赫赛汀的BBB靶向纳米颗粒也引起相当大的抗肿瘤活性。这些结果证明了靶向纳米粒子系统在整个BBB / BTB中单独或与其他药物联合递送抗体以改善治疗效果的潜力。