Department of Life Sciences, Pohang University of Science and Technology, Pohang 37673, Republic of Korea.
Department of Life Sciences, Pohang University of Science and Technology, Pohang 37673, Republic of Korea.
Biomaterials. 2017 Jan;113:68-79. doi: 10.1016/j.biomaterials.2016.10.037. Epub 2016 Oct 26.
Increasing incidents of patients diagnosed with cancer have brought massive improvement in the delivery technologies to help patients receiving chemotherapy. However, tumor specific targeting of the chemotherapeutics still remains as a challenge mainly due to the difficulties in the conjugation and manipulation of bio-specific molecules on the surface. Herein, we genetically engineered bacterial protoplast to develop nanovesicles having no toxic outer membrane components that can specifically target and deliver chemotherapeutics to tumor tissues. The bacterial protoplast nanovesicles expressing tumor-targeting moieties on the surface were prepared by serial extrusions through nano-sized membrane filters. The nano-sized vesicular structure of protoplast nanovesicles offers passive targeting to solid tumor site and expression of tumor-targeting moiety enhance tumor-specific uptake via receptor-mediated targeting. Chemotherapeutics-loaded in the nanovesicles induce dose-dependent cytotoxicity in tumor cells in vitro. Moreover, specific trafficking of drug-loaded nanovesicles to the tumor tissue and efficient prevention of tumor growth in tumor xenografted mice are shown. Importantly, this tumor growth suppression of protoplast nanovesicles has shown to reduce the chemotherapeutics-induced adverse effects after systemic administration to mice. This study offers great potential of protoplast nanovesicles as effective and safe delivery system to optimize and contribute to the development of advanced chemotherapy.
越来越多的癌症患者被诊断出来，这促使化疗输送技术得到了巨大的改进。然而，由于在表面上连接和操作生物特异性分子的困难，肿瘤特异性靶向化疗仍然是一个挑战。在这里，我们通过基因工程将细菌原生质体转化为纳米囊泡，这些纳米囊泡没有有毒的外膜成分，可以特异性地靶向并将化疗药物递送到肿瘤组织中。通过纳米尺寸的膜过滤器进行多次挤压，制备出表面表达肿瘤靶向部分的细菌原生质体纳米囊泡。原生质体纳米囊泡的纳米尺寸囊泡结构为实体瘤部位提供被动靶向，并且通过受体介导的靶向作用增强肿瘤特异性摄取表达的肿瘤靶向部分。载有化疗药物的纳米囊泡在体外对肿瘤细胞表现出剂量依赖性细胞毒性。此外，研究还表明，载药纳米囊泡能够特异性地向肿瘤组织运输，并有效地防止肿瘤异种移植小鼠的肿瘤生长。重要的是，这种原生质体纳米囊泡对肿瘤生长的抑制作用表明，它可以减少化疗药物全身给药后对小鼠产生的不良反应。这项研究为原生质体纳米囊泡作为有效的、安全的递药系统提供了巨大的潜力，可以优化并有助于先进化疗的发展。
