Crystal-Seeded Growth of pH-Responsive Metal-Organic Frameworks for Enhancing Encapsulation, Stability, and Bioactivity of Hydrophobicity Compounds

Zeolitic imidazolate framework-L (ZIF-L) could effectively improve the stability, controlled release, and anticancer activity of natural hydrophobicity drugs in drug delivery systems (DDSs). A simple and universal strategy was developed to prepare the curcumin-loaded ZIF-L (CCM@ZIF-L) by the antisolvent coprecipitation method, which was different from the traditional approaches. The microcrystal molecules of curcumin were used as the core of ZIF-L growth to form CCM@ZIF-L, which has a very high drug encapsulation efficiency of 98.21% and a regular leaf or cruciate flower-like structure. The formation of CCM@ZIF-L with a distinct composite structure was supported by scanning electron microscopy, transmission electron microscopy, Fourier-transform infrared, powder X-ray diffraction, and zeta-potential. Because of the protective effect of ZIF-L, CCM@ ZIF-L exhibited excellent stability and about a 5-fold increase in temperature stability over free curcumin. CCM@ZIF-L exhibited controlled drug release behavior in simulated in vitro tumor microenvironments (almost 81.2% drug release over a period of 72 h). Furthermore, confocal laser scanning microscopy results and cytotoxicity experiments confirmed that the encapsulated curcumin showed a significant improvement in cellular uptake and anticancer activity against A549 cancer cells. Moreover, the curcumin encapsulated in ZIF-L exhibited remarkable cellular antioxidant activity based on MGC-803 cell models. This work presents a novel approach to solve the drug loading problem by employing ZIF-L and exhibits enormous potential of ZIF-L as an effective DDS in cancer treatments.