Construction and evaluation of a DOX@MOF-199-PDA–HA nanoparticle drug delivery system

Abstract

Metal–organic frameworks (MOFs) are a unique class of coordination polymers characterized by their high porosity and enormous specific surface area, which enable their use as carriers. We have constructed a novel MOF-based nanodelivery system designed for multimodal combination therapy to enhance the delivery efficiency and efficacy of chemotherapeutic drugs. MOF-199, which inherently possesses a drug-release response function, was used as a nanodrug carrier. Doxorubicin (DOX) was encapsulated through physical adsorption, and the carrier surface was modified with a biomimetic material, polydopamine (PDA). Both PDA and hyaluronic acid (HA) molecules contain carboxyl groups, which can be connected through Fe³⁺-mediated coordination interactions. Transmission electron microscopy (TEM) and dynamic light scattering (DLS) were used to test the size, dispersity, and structural characteristics of the synthesized products, confirming their appropriate size and dispersity. BET (BET surface area) and TGA test results indicated that the nanocarrier exhibits good stability, a large specific surface area, and high porosity, making it suitable for use as a drug carrier. Ultraviolet spectrophotometry confirmed that the nanocarrier MOF-199-PDA–HA has the ability to consume GSH, with the drug loading rate and encapsulation efficiency of DOX in the system measured as 39.58% and 73.26%, respectively. In cellular experiments, the DOX@MOF-199-PDA–HA group produced toxic hydroxyl radicals following H₂O₂ addition. After near-infrared light irradiation, both cellular toxicity and reactive oxygen species fluorescence intensity increased, indicating further enhanced anticancer efficacy. Using free HA as a control, it was confirmed that HA enhances tumor-specific accumulation of DOX@MOF-199-PDA–HA by binding to CD44 receptors on cancer cell surfaces. DOX@MOF-199-PDA–HA is a pH/GSH/NIR-responsive nanodelivery system with targeting function. This system ensures that drugs are released with higher efficiency in the tumor microenvironment through pH and glutathione (GSH) responsive drug-release mechanisms, thereby reducing toxicity to healthy tissues.