Gemcitabine-monophosphate encapsulation in “stealth” MOFs effectively inhibits tumor growth in vivo

Abstract

Gemcitabine is a commonly used chemotherapeutic agent that faces limitations due to rapid clearance, limited stability, and significant adverse effects. Recent efforts in its nanoencapsulation within Metal Organic Frameworks (MOFs) aim to overcome these barriers, offering a promising platform due to MOFs’ high drug-loading capacity, green synthesis methods, and in vivo biocompatibility. This study further explores the use of dextran-alendronate-PEG (DAP) coating to enhance MOF colloidal stability while maintaining substantial drug loading in the MOFs. Here, we demonstrate that DAP is essential for preventing the degradation of MOFs and enhancing their colloidal stability, enabling them to evade the mononuclear phagocytic system. The results also confirm that a high gemcitabine drug loading is preserved in DAP-coated MOFs. Furthermore, encapsulation improves the efficacy of the drug, as evidenced by a threefold decrease in the IC50 in prostate cancer cells compared to the free drug. Additionally, the use of the chorioallantoic membrane (CAM) assay, an alternative in vivo preclinical model, confirms that only gemcitabine-loaded MOFs effectively inhibit tumor growth. This work provides valuable insights into a biocompatible drug delivery system that improves the stability and therapeutic outcomes of gemcitabine in biological environments