Biotinylated Mn₃O₄ nanocuboids for targeted delivery of gemcitabine hydrochloride to breast cancer and MRI applications

Multifunctional nanocarriers have been found as potential candidate for the targeted drug delivery and imaging applications. Herein, we have developed a biocompatible and pH-responsive manganese oxide nanocuboid system, surface modified with poly (ethylene glycol) bis(amine) and functionalized with biotin (Biotin-PEG-MNCs), for an efficient and targeted delivery of an anticancer drug (gemcitabine, GEM) to the human breast cancer cells. GEM-loaded Biotin-PEG@MNCs showed high drug loading efficiency, controlled release of GEM and excellent storage stability in the physiological buffers and different temperature conditions. GEM-loaded Biotin-PEG@MNCs showed dose- and time-dependent decrease in the viability of human breast cancer cells. Further, it exhibited significantly higher cell growth inhibition than pure GEM which suggested that Biotin-PEG@MNCs has efficiently delivered the GEM into cancerous cells. The role of biotin in the uptake was proved by the competitive binding-based cellular uptake study. A significant decrease in the amount of manganese was observed in biotin pre-treated cancer cells as compared to biotin untreated cancer cells. In MRI studies, Biotin-PEG-MNCs showed both longitudinal and transverse relaxivity about 0.091 and 7.66 mM⁻¹ s⁻¹ at 3.0 T MRI scanner, respectively. Overall, the developed Biotin-PEG-MNCs presents a significant potential in formulation development for cancer treatment via targeted drug delivery and enhanced MRI contrast imaging properties.