Instituto de Investigación Sanitaria de Aragón (IIS Aragón), Avda. San Juan Bosco, 13, 50009 Zaragoza, Spain.
Instituto de Nanociencia y Materiales de Aragón (INMA), CSIC-Universidad de Zaragoza, Campus Rio Ebro, Edificio I+D, C/Poeta Mariano Esquillor, s/n, 50018 Zaragoza, Spain.
Cells. 2024 Apr 16;13(8):691. doi: 10.3390/cells13080691.
Several studies have reported the successful use of bio-orthogonal catalyst nanoparticles (NPs) for cancer therapy. However, the delivery of the catalysts to the target tissues in vivo remains an unsolved challenge. The combination of catalytic NPs with extracellular vesicles (EVs) has been proposed as a promising approach to improve the delivery of therapeutic nanomaterials to the desired organs. In this study, we have developed a nanoscale bio-hybrid vector using a CO-mediated reduction at low temperature to generate ultrathin catalytic Pd nanosheets (PdNSs) as catalysts directly inside cancer-derived EVs. We have also compared their biodistribution with that of PEGylated PdNSs delivered by the EPR effect. Our results indicate that the accumulation of PdNSs in the tumour tissue was significantly higher when they were administered within the EVs compared to the PEGylated PdNSs. Conversely, the amount of Pd found in non-target organs (i.e., liver) was lowered. Once the Pd-based catalytic EVs were accumulated in the tumours, they enabled the activation of a paclitaxel prodrug demonstrating their ability to carry out bio-orthogonal uncaging chemistries in vivo for cancer therapy.
已有多项研究报告称，生物正交催化剂纳米颗粒（NPs）可成功用于癌症治疗。然而，将催化剂递送至体内靶组织仍然是一个尚未解决的挑战。将催化 NPs 与细胞外囊泡（EVs）结合已被提出是一种很有前途的方法，可提高治疗性纳米材料向所需器官的递送。在本研究中，我们开发了一种纳米级生物杂交载体，通过 CO 介导的低温还原反应，直接在源自癌症的 EVs 内生成超薄的催化 Pd 纳米片（PdNSs）作为催化剂。我们还比较了它们的生物分布与通过 EPR 效应递送的 PEG 化 PdNSs 的生物分布。结果表明，与 PEG 化 PdNSs 相比，当将 PdNSs 包裹在 EVs 中给药时，其在肿瘤组织中的积累明显更高。相反，在非靶器官（即肝脏）中发现的 Pd 量降低。一旦基于 Pd 的催化 EVs 在肿瘤中积累，它们就能够激活紫杉醇前药，证明它们能够在体内进行生物正交解笼化化学，用于癌症治疗。
