Biomedical Sciences Research Institute, University of Ulster , Coleraine, Northern Ireland BT52 1SA, United Kingdom.
Langmuir. 2014 Dec 16;30(49):14926-30. doi: 10.1021/la503929c. Epub 2014 Dec 2.
Microbubbles (MBs) have recently emerged as promising delivery vehicles for sensitizer drugs in sonodynamic therapy (SDT). The ability to selectively destroy the MB and activate the sensitizer using an external ultrasound trigger could provide a minimally invasive and highly targeted therapy. While lipid MBs have been approved for use as contrast agents in diagnostic ultrasound, the attachment of sensitizer drugs to their surface results in a significant reduction in particle stability. In this Article, we prepare both lipid and polymer (PLGA) MBs with rose bengal attached to their surface and demonstrate that PLGA MB conjugates are significantly more stable than their lipid counterparts. In addition, the improved stability offered by the PLGA shell does not hinder their selective destruction using therapeutically acceptable ultrasound intensities. Furthermore, we demonstrate that treatment of ectopic human tumors (BxPC-3) in mice with the PLGA MB-rose bengal conjugate and ultrasound reduced tumor volume by 34% 4 days after treatment while tumors treated with the conjugate alone increased in volume by 48% over the same time period. Therefore, PLGA MBs may offer a more stable alternative to lipid MBs for the site specific delivery of sensitizers in SDT.
微泡（MBs）最近作为声动力学治疗（SDT）中敏化剂药物的有前途的递送载体出现。使用外部超声触发选择性地破坏 MB 并激活敏化剂的能力可以提供一种微创且高度靶向的治疗方法。虽然脂质 MB 已被批准用作诊断超声中的造影剂，但将敏化剂药物附着在其表面会导致颗粒稳定性显著降低。在本文中，我们制备了表面附着有玫瑰红的脂质和聚合物（PLGA）MB，并证明 PLGA MB 缀合物比其脂质对应物稳定得多。此外，PLGA 壳提供的稳定性提高不会阻碍使用治疗上可接受的超声强度选择性地破坏它们。此外，我们证明用 PLGA MB-玫瑰红缀合物和超声治疗小鼠异位人肿瘤（BxPC-3）可在治疗后 4 天使肿瘤体积减少 34%，而单独用缀合物治疗的肿瘤在同一时间段内体积增加了 48%。因此，PLGA MB 可能为 SDT 中敏化剂的定点递供提供比脂质 MB 更稳定的替代物。
