Desai Omkar, Köster Mario, Kloos Doreen, Lachmann Nico, Hauser Hansjörg, Poortinga Albert, Wirth Dagmar
Model System for Infection and Immunity, Helmholtz Centre for Infection Research, Braunschweig, Germany.
Department of Pediatric Pneumology, Allergology and Neonatology, Hannover Medical School, 30625 Hannover, Germany.
J Control Release. 2025 Feb 10;378:365-376. doi: 10.1016/j.jconrel.2024.12.007. Epub 2024 Dec 19.
Nanoparticles have proven to be attractive carriers in therapeutic drug delivery since they can encapsulate, protect and stabilize a plethora of different drugs, thereby improving therapeutic efficacy and reducing side effects. However, specific targeting of drug-loaded nanoparticles to the tissue of interest and a timely and spatially controlled release of drugs on demand still represent a challenge. Recently, gas-filled microparticles, so-called antibubbles, have been developed which can efficiently encapsulate liquid drug droplets. Here, we show that antibubbles are efficiently taken up by macrophages in vitro and are stably maintained for more than 48 h without compromising antibubble integrity and macrophage viability. We show that application of diagnostic ultrasound induces the disintegration of both antibubbles and carrier cells while not affecting non-loaded macrophages. Using 4-hydroxytamoxifen as a model drug, we show ultrasound-mediated drug release upon adoptive transfer of antibubble-loaded macrophages in mice. Together with the ability of macrophages to accumulate in inflamed tissues, antibubble-loaded macrophages represent an attractive tool for targeted delivery of drugs and its ultrasound-mediated spatial and temporal drug release, highlighting the therapeutic perspective of this strategy.
纳米颗粒已被证明是治疗性药物递送中极具吸引力的载体，因为它们可以包裹、保护并稳定大量不同的药物，从而提高治疗效果并减少副作用。然而，将载药纳米颗粒特异性靶向到感兴趣的组织，并根据需要及时、在空间上可控地释放药物，仍然是一项挑战。最近，已开发出所谓的抗气泡充气微粒，其可以有效地包裹液体药物滴。在此，我们表明抗气泡在体外能被巨噬细胞有效摄取，并能稳定维持超过48小时，而不会损害抗气泡完整性和巨噬细胞活力。我们表明，应用诊断超声会诱导抗气泡和载体细胞解体，同时不影响未负载的巨噬细胞。使用4-羟基他莫昔芬作为模型药物，我们展示了在小鼠体内过继转移负载抗气泡的巨噬细胞后，超声介导的药物释放。结合巨噬细胞在炎症组织中积累的能力，负载抗气泡的巨噬细胞是一种有吸引力的工具，可用于药物的靶向递送及其超声介导的时空药物释放，突出了该策略的治疗前景。
