Discovery of valley-hill structures on the surface of MOFs: Enhancing DOX diffusion and release through nature-made channels

On the afternoon of October 14, 2020, we serendipitously discovered a novel “valley-hill” structure on the surface of a Metal-Organic Framework (MOF) after mixing it with a solution of tangerine peel extract (L) in the laboratory. This unexpected observation led to the formation of channels within the MOF surface and significantly improved release performance, particularly with doxorubicin (DOX). The unique valley-hill morphology and the resultant channels facilitated exceptional DOX diffusion into the MOF's porosity. Building on this structure, we systematically engineered the A520 (aluminum fumarate) MOF using green chemistry methodologies in a dual-stage process, incorporating L as a natural polymer blend matrix to create efficient DOX delivery platforms, A520@L@DOX and A520@L@DOX@L. These innovative constructs exhibited remarkable drug diffusion, diagnostic, and therapeutic attributes. The dual application of initial and secondary coating layers was crucial in controlling drug release and reducing cytotoxicity, especially in acidic cellular environments. Cell viability assessments conducted on HEK-293, HeLa, MCF-7, and PC12 ​cell lines after 24-h and 48-h exposures to varying concentrations (0.1 μg/mL to 50 ​μg/mL) of A520@L@DOX@L demonstrated high cell viability percentages: 98.2 ​% and 97.1 ​% at 24-h, and 96.5 ​% and 92.1 ​% at 48-h, respectively. Comparative analyses between the cytotoxic effects of A520@L@DOX and A520@L@DOX@L formulations highlighted the distinctive functionalities imparted by the green coatings, including mitigated toxicity, regulated drug discharge kinetics, and pH-responsive drug delivery. To visualize the behavior of drug-loaded nanocarriers in microenvironments, DAPI-stained MCF-7 ​cells were subjected to 2D fluorescence microscopy.