Department of Chemistry, National Taiwan University, Taipei, Taiwan.
Molecular Science and Technology Program, Taiwan International Graduate Program, Institute of Atomic and Molecular Sciences, Academia Sinica, Taipei, Taiwan.
Biomaterials. 2015 Jan;37:436-46. doi: 10.1016/j.biomaterials.2014.10.006. Epub 2014 Oct 23.
Developing novel multifunctional nanoparticles (NPs) with robust preparation, low cost, high stability, and flexible functionalizability is highly desirable. This study provides an innovative platform, termed unibody core-shell (UCS), for this purpose. UCS is comprised of two covalent-bonded polymers differed only by the functional groups at the core and the shell. By conjugating Gd(3+) at the stable core and encapsulating doxorubicin (Dox) at the shell in a pH-sensitive manner, we developed a theranostic NPs (UCS-Gd-Dox) that achieved a selective drug release (75% difference between pH 7.4 and 5.5) and MR imaging (r1 = 0.9 and 14.5 mm(-1) s(-1) at pH 7.4 and 5.5, respectively). The anti-cancer effect of UCS-Gd-Dox is significantly better than free Dox in tumor-bearing mouse models, presumably due to enhanced permeability and retention effect and pH-triggered release. To the best of our knowledge, this is the simplest approach to obtain the theranostic NPs with Gd-conjugation and Dox doping.
开发具有稳健制备、低成本、高稳定性和灵活功能化的新型多功能纳米粒子(NPs)是非常可取的。本研究为此提供了一个创新平台,称为单体核壳(UCS)。UCS 由两种仅在核和壳处的官能团不同的共价键合聚合物组成。通过在稳定核处结合 Gd(3+)并以 pH 敏感的方式在壳处包封阿霉素(Dox),我们开发了一种治疗诊断 NPs(UCS-Gd-Dox),实现了选择性药物释放(pH 值为 7.4 和 5.5 之间的差异为 75%)和磁共振成像(r1 值分别为 0.9 和 14.5mm(-1)s(-1),pH 值分别为 7.4 和 5.5)。与游离 Dox 相比,UCS-Gd-Dox 在荷瘤小鼠模型中的抗癌效果明显更好,可能是由于增强的通透性和保留效应以及 pH 触发的释放。据我们所知,这是获得具有 Gd 结合和 Dox 掺杂的治疗诊断 NPs 的最简单方法。