Emodin regulates nucleation and crystal growth of ZIF-8 for developing the size-dependent nanotherapeutics

The particle size of ZIF-8 significantly influences its benefits in drug delivery and release, thereby determining therapeutic efficacy. Here, we investigate the correlations between drugs and ZIF-8 crystallization and discover that emodin can function as a binding template for zinc ions to accelerate nucleation processes via reducing the Gibbs free energy, while also serving as a capping agent on the {100} facets to regulate crystal growth. These dual roles, based on hydroxyl-substituted anthraquinone structure of emodin, can govern ZIF-8 crystallization, enabling the precise control over both size and morphology of emodin-loaded ZIF-8 (E@Z). Consequently, by regulating the feed ratio of emodin, E@Z ranging in size from 900 nm to 80 nm are successfully prepared. The therapeutic outcomes demonstrate that, in addition to enhancing the antibacterial effect of emodin, size-dependent degradation properties of E@Z enable a controlled release of emodin within tumor, ultimately amplifying its anti-tumor efficacy. Additionally, other natural anthraquinones compounds with structures similar to emodin also possess this ability to regulate ZIF-8 size. Our study provides a fundamental framework for the advancement of anthraquinone drugs and their potential applications in the field of ZIF-8-based size-dependent nanotherapeutics.