Free-Standing Hierarchically Porous Silica Nanoparticle Superstructures: Bridging the Nano- to Microscale for Tailorable Delivery of Small and Large Therapeutics
Free-Standing Hierarchically Porous Silica Nanoparticle Superstructures: Bridging the Nano- to Microscale for Tailorable Delivery of Small and Large Therapeutics
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DOI：
10.1021/acsami.3c16463
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发表时间：
2024-01-25
影响因子：
9.5
通讯作者：
Ong，Zhan Yuin
中科院分区：
文献类型：
--
作者：
Palvai，Sandeep;Kpeglo，Delanyo;Ong，Zhan Yuin
纳米尺度的胶体自组装是一种令人兴奋的方法，可以产生具有不同于单个纳米粒子的性质的超结构。然而，自下而上的三维纳米粒子超结构的自组装通常需要广泛的化学官能化，苛刻的条件，以及较长的准备时间，这对于生物医学应用是不可取的。在这里，我们报道了定向冷冻多孔二氧化硅纳米颗粒(PSiNPs)作为一种简单而通用的技术来创建各向异性的3D超结构，该结构具有由微孔PSiNPs和在PSiNPs之间新产生的中孔和大孔提供的分层孔道。通过改变PSiNP构建块的大小，可以很容易地调整颗粒间的孔大小。新产生的分级孔极大地增加了小分子抗癌药物阿霉素(Dox)和大分子溶菌酶(Lyz)的负载量。重要的是，负载到纳米颗粒组件的微孔和中孔/大孔中的Dox不仅提供了依赖于孔大小的药物释放，而且与仅加载到微孔或中孔/大孔中的Dox相比，药物释放显著延长到25天，而药物释放的时间要短得多。此外，还观察到了独特的药物释放时间分布，从较大的颗粒间大孔释放Lyz比从较小的PSiNP微孔释放Dox更高和更快。最后，复合水凝胶中负载Dox的超结构的配方在3D椭圆形胰腺导管腺癌模型中诱导了长期的生长抑制。这项研究提出了一种简便的模块化方法，用于在全水环境中快速组装载药超结构，并展示了它们作为高度可定制和可持续输送系统用于各种治疗的潜力。
Nanoscale colloidal self-assembly is an exciting approach to yield superstructures with properties distinct from those of individual nanoparticles. However, the bottom-up self-assembly of 3D nanoparticle superstructures typically requires extensive chemical functionalization, harsh conditions, and a long preparation time, which are undesirable for biomedical applications. Here, we report the directional freezing of porous silica nanoparticles (PSiNPs) as a simple and versatile technique to create anisotropic 3D superstructures with hierarchical porosity afforded by microporous PSiNPs and newly generated meso- and macropores between the PSiNPs. By varying the PSiNP building block size, the interparticle pore sizes can be readily tuned. The newly created hierarchical pores greatly augment the loading of a small molecule-anticancer drug, doxorubicin (Dox), and a large macromolecule, lysozyme (Lyz). Importantly, Dox loading into both the micro- and meso/macropores of the nanoparticle assemblies not only gave a pore size-dependent drug release but also significantly extended the drug release to 25 days compared to a much shorter 7 or 11 day drug release from Dox loaded into either the micro- or meso/macropores only. Moreover, a unique temporal drug release profile, with a higher and faster release of Lyz from the larger interparticle macropores than Dox from the smaller PSiNP micropores, was observed. Finally, the formulation of the Dox-loaded superstructures within a composite hydrogel induces prolonged growth inhibition in a 3D spheroid model of pancreatic ductal adenocarcinoma. This study presents a facile modular approach for the rapid assembly of drug-loaded superstructures in fully aqueous environments and demonstrates their potential as highly tailorable and sustained delivery systems for diverse therapeutics.