Department of Chemistry and CSGI, University of Florence , Via della Lastruccia 3, 50019-Sesto Fiorentino, Florence, Italy.
ACS Nano. 2016 Aug 23;10(8):7749-60. doi: 10.1021/acsnano.6b03194. Epub 2016 Aug 12.
The simultaneous or sequential delivery of multiple therapeutic active principles to a specific target is one of the main challenges of nanomedicine. This goal requires the construction of complex devices often extremely time and cost consuming. Supramolecular self-assemblies, with building blocks of different nature, each providing a specific function to the final construct, can combine a facile synthetic route with a high tunability and structural control. In this study we provide the proof-of-principle of a drug delivery system, DDS, constituted of (i) liposomes, providing a fully biocompatible lipid scaffold suitable to host both hydrophobic and hydrophilic drugs; (ii) a double-stranded DNA conjugated with a cholesteryl unit that spontaneously inserts into the lipid membrane; and (iii) hydrophobic and hydrophilic superparamagnetic iron oxide nanoparticles (SPIONs) embedded inside the lipid membrane of liposomes or connected to the DNA, respectively. Upon application of an alternating magnetic field, the SPIONs can trigger, through thermal activation, the release of a DNA strand or of the liposomal payload, depending on the frequency and the application time of the field, as proved by both steady-state and time-resolved fluorescence studies. This feature is due to the different localization of the two kinds of SPIONS within the construct and demonstrates the feasibility of a multifunctional DDS, built up from self-assembly of biocompatible building blocks.
将多种治疗活性药物同时或顺序递送至特定靶点是纳米医学的主要挑战之一。这一目标需要构建复杂的设备，通常非常耗时且昂贵。具有不同性质的构建模块的超分子自组装，每个构建模块都为最终构建体提供特定的功能，可以将简便的合成路线与高可调和结构控制结合起来。在本研究中，我们提供了一种由（i）脂质体提供的药物递送系统（DDS）的原理证明，脂质体提供了完全生物相容的脂质支架，适合容纳疏水性和亲水性药物；（ii）与胆固醇单元缀合的双链 DNA，该单元可自发插入脂质膜；以及（iii）嵌入脂质体的疏水性和亲水性超顺磁性氧化铁纳米粒子（SPIONs）或分别连接到 DNA。施加交变磁场后，SPIONs 可通过热激活触发 DNA 链或脂质体有效载荷的释放，这取决于磁场的频率和施加时间，这一点通过稳态和时间分辨荧光研究得到了证明。这一特性归因于两种 SPIONs 在构建体中的不同定位，证明了由生物相容性构建模块自组装构建多功能 DDS 的可行性。
