Mitoxantrone-Derivative Drug Structure-Directing Agent for the Synthesis of Magnetic Mesoporous Silica Nanoparticles for Breast Cancer Treatment

Abstract

Cancer causes hundreds of thousands of deaths worldwide each year. Chemotherapy, the treatment of choice for invasive cancers, presents severe side effects related to off-target exposure that limit its dosage and, thus, its efficacy. Nanomedicine has emerged as a potential tool to overcome these problems. Among the nanocarriers, mesoporous silica nanoparticles (MSNs) have attracted much attention due to their high surface area (up to 1000 m2 g–1), the versatility in size and pore diameter, and their ease of functionalization. However, drug leakage from the MSNs usually occurs before the nanocarriers reach their target, reducing drug efficacy and causing adverse effects. Our group has developed a promising method to increase drug loading capacity while preventing premature drug release. This strategy consists of the use of a drug structure-directing agent (DSDA) that plays a dual role, acting as a pharmacological prodrug and as a template for the synthesis of MSNs. Here, we successfully synthesized a DSDA from the anticancer drug mitoxantrone (MTO), which is used in clinical practice for the treatment of metastatic breast cancer, and used it to synthesize magnetic MSNs whose porosity was fully filled with the MTO prodrug (magnetic MTO-C12@MSNs). The release behavior was pH-dependent, showing negligible drug release at physiological pH and a significant increase at the pH of the tumoral microenvironment. Finally, the efficacy of magnetic MTO-C12@MSNs in reducing breast cancer cell viability was confirmed, demonstrating the potential of this material as an efficient drug delivery system to target breast cancer tumors while avoiding side effects.