Department of Chemistry, University of Alabama at Birmingham, Birmingham, Alabama 35294, United States.
Center for Nanomaterials and Biointegration, University of Alabama at Birmingham, Birmingham, Alabama 35294, United States.
ACS Appl Mater Interfaces. 2020 Dec 23;12(51):56792-56804. doi: 10.1021/acsami.0c17456. Epub 2020 Dec 11.
Radionuclide-functionalized drug delivery vehicles capable of being imaged positron emission tomography (PET) are of increasing interest in the biomedical field as they can reveal the behavior of encapsulated therapeutics with high sensitivity. However, the majority of current PET-guided theranostic agents suffer from poor retention of radiometal over time, low drug loading capacities, and time-limited PET imaging capability. To overcome these challenges, we have developed hollow microcapsules with a thin (<100 nm) multilayer shell as advanced theranostic delivery systems for multiday PET tracking . The 3 μm capsules were fabricated the aqueous multilayer assembly of a natural antioxidant, tannic acid (TA), and a poly(-vinylpyrrolidone) (PVPON) copolymer containing monomer units functionalized with deferoxamine (DFO) to chelate the Zr radionuclide, which has a half-life of 3.3 days. We have found using radiochromatography that (TA/PVPON-DFO) capsules retained on average 17% more Zr than their (TA/PVPON) counterparts, which suggests that the covalent attachment of the DFO to PVPON provides stable Zr chelation. PET imaging studies performed in mice demonstrated that excellent stability and imaging contrast were still present 7 days postinjection. Animal biodistribution analyses showed that capsules primarily accumulated in the spleen, liver, and lungs with negligible accumulation in the femur, with the latter confirming the stable binding of the radiotracer to the capsule walls. The application of therapeutic ultrasound (US) (60 s of 20 kHz US at 120 W cm) to Zr-functionalized capsules could release the hydrophilic anticancer drug doxorubicin from the capsules in the therapeutic amounts. Polymeric capsules with the capability of extended PET-based tracking and US-induced drug release provide an advanced platform for development of precision-targeted therapeutic carriers and could aid in the development of more effective drug delivery systems.
可通过正电子发射断层扫描 (PET) 成像的放射性核素功能化药物递送载体在生物医学领域越来越受到关注，因为它们能够以高灵敏度揭示封装治疗剂的行为。然而，目前大多数的 PET 引导治疗剂都存在放射性金属随时间保留不佳、药物载药量低和 PET 成像能力有限的问题。为了克服这些挑战，我们开发了具有薄 (<100nm) 多层壳的空心微胶囊，作为用于多日 PET 跟踪的先进治疗性递药系统。3μm 胶囊是通过天然抗氧化剂鞣酸 (TA) 和含有单体单元的聚(-乙烯基吡咯烷酮) (PVPON) 共聚物的水相多层组装来制造的，这些单体单元用去铁胺 (DFO) 功能化以螯合 Zr 放射性核素，其半衰期为 3.3 天。我们通过放射性色谱法发现，(TA/PVPON-DFO) 胶囊平均保留了比 (TA/PVPON) 胶囊多 17%的 Zr，这表明 DFO 与 PVPON 的共价连接提供了稳定的 Zr 螯合。在小鼠中进行的 PET 成像研究表明，在注射后 7 天，仍存在极好的稳定性和成像对比度。动物生物分布分析表明，胶囊主要在脾脏、肝脏和肺部积累，在股骨中几乎没有积累，后者证实了放射性示踪剂与胶囊壁的稳定结合。将治疗性超声 (US)（60s 的 20kHz US，强度为 120Wcm）应用于 Zr 功能化胶囊可以将亲水性抗癌药物阿霉素从胶囊中以治疗量释放出来。具有基于 PET 的延长跟踪和 US 诱导的药物释放能力的聚合物胶囊为开发精密靶向治疗载体提供了一个先进的平台，并有助于开发更有效的药物输送系统。
