Department of Nanoengineering, University of California San Diego, La Jolla, CA, 92093, USA.
Adv Mater. 2020 Jun;32(25):e2000091. doi: 10.1002/adma.202000091. Epub 2020 May 17.
A tubular micromotor with spatially resolved compartments is presented toward efficient site-specific cargo delivery, with a back-end zinc (Zn) propellant engine segment and an upfront cargo-loaded gelatin segment further protected by a pH-responsive cap. The multicompartment micromotors display strong gastric-powered propulsion with tunable lifetime depending on the Zn segment length. Such propulsion significantly enhances the motor distribution and retention in the gastric tissues, by pushing and impinging the front-end cargo segment onto the stomach wall. Once the micromotor penetrates the gastric mucosa (pH ≥ 6.0), its pH-responsive cap dissolves, promoting the autonomous localized cargo release. The fabrication process, physicochemical properties, and propulsion behavior are systematically tested and discussed. Using a mouse model, the multicompartment motors, loaded with a model cargo, demonstrate a homogeneous cargo distribution along with approximately four-fold enhanced retention in the gastric lining compared to monocompartment motors, while showing no apparent toxicity. Therapeutic payloads can also be loaded into the pH-responsive cap, in addition to the gelatin-based compartment, leading to concurrent delivery and sequential release of dual cargos toward combinatorial therapy. Overall, this multicompartment micromotor system provides unique features and advantages that will further advance the development of synthetic micromotors for active transport and localized delivery of biomedical cargos.
本文提出了一种具有空间分辨隔室的管状微马达,用于高效的靶向货物输送,其后端有一个锌(Zn)推进剂引擎段,前端是负载货物的明胶段,进一步由 pH 响应帽保护。多隔室微马达在胃动力的推动下表现出强推进力,其寿命可通过 Zn 段长度进行调节。这种推进力显著增强了马达在胃组织中的分布和保留,通过将前端货物段推压到胃壁上。一旦微马达穿透胃黏膜(pH≥6.0),其 pH 响应帽溶解,促进自主局部货物释放。系统测试和讨论了制造工艺、物理化学性质和推进行为。使用小鼠模型,负载模型货物的多隔室马达在胃衬里中的分布均匀,与单隔室马达相比,保留时间延长了约四倍,同时没有明显的毒性。除了基于明胶的隔室外,还可以将治疗性有效载荷装入 pH 响应帽中,从而实现双重货物的同时递药和顺序释放,以进行联合治疗。总体而言,这种多隔室微马达系统具有独特的特点和优势,将进一步推动用于生物医学货物主动输送和局部递送的合成微马达的发展。