Xu Wenzhe, Chen Yang, Yang Ruixu, Fu Yiying, Zhuang Wanxin, Wang Yonggang, Liu Yi, Zhang Hao
State Key Laboratory of Supramolecular Structure and Materials, College of Chemistry, Jilin University, Changchun 130012, P. R. China.
Department of Cardiovascular Centre, The First Hospital of Jilin University, Changchun 130021, P. R. China.
ACS Nano. 2023 Sep 26;17(18):18227-18239. doi: 10.1021/acsnano.3c05229. Epub 2023 Sep 5.
Nanoprecipitation, which is achieved through the diffusion and precipitation of drug molecules in blended solvent and antisolvent phases, is a classic route for constructing nanodrugs (NDs) and previously directed by diffusion-controlled theory. However, the diffusion-controlled mechanism is out of date in the recent preparation of self-delivery supramolecular NDs (SDSNDs), characterized by the construction of drug nanoparticles through supramolecular interactions in the absence of carriers and surfactants. Herein, a "reaction"-like complement, contributed from supramolecular interactions, is proposed for the preparation of naphthoquinone SDSNDs. Different from the diffusion-controlled process, the formation rate of SDSNDs via the "reaction"-like process is almost constant and highly dependent on the supramolecular interaction-determined Gibbs free energy of molecular binding. Thus, the formation rate and drug availability of SDSNDs are greatly improved by engineering the supramolecular interactions, which facilitates the preparation of SDSNDs with expected sizes, components, and therapeutic functions. As a deep understanding of supramolecular-interaction-involved nanoprecipitation, the current "reaction"-like protocol not only provides a theoretical supplement for classic nanoprecipitation but also highlights the potential of nanoprecipitation in shaping self-assembled, coassembled, and metal-ion-associated SDSNDs.
纳米沉淀是通过药物分子在混合溶剂和反溶剂相中扩散和沉淀来实现的，是构建纳米药物（NDs）的经典途径，此前由扩散控制理论指导。然而，在最近制备的自递送超分子纳米药物（SDSNDs）中，扩散控制机制已过时，其特点是在没有载体和表面活性剂的情况下通过超分子相互作用构建药物纳米颗粒。在此，提出了一种由超分子相互作用贡献的类似“反应”的补充方法来制备萘醌SDSNDs。与扩散控制过程不同，通过类似“反应”过程形成SDSNDs的速率几乎是恒定的，并且高度依赖于超分子相互作用确定的分子结合吉布斯自由能。因此，通过设计超分子相互作用，SDSNDs的形成速率和药物可用性得到了极大提高，这有助于制备具有预期尺寸、成分和治疗功能的SDSNDs。作为对涉及超分子相互作用的纳米沉淀的深入理解，当前类似“反应”的方案不仅为经典纳米沉淀提供了理论补充，还突出了纳米沉淀在塑造自组装、共组装和金属离子相关SDSNDs方面的潜力。
