Curcumin/sunitinib co-loaded BSA-stabilized SPIOs for synergistic combination therapy for breast cancer

Abstract

Coating supermagnetic iron oxide nanoparticles (SPIOs) with albumin would not only improve their in vivo stability but also improve their drug loading capacity, but current methods are either inefficient or time consuming. Herein, a single step synthesis of bovine serum albumin (BSA)-stabilized SPIOs with high dispersity and stability via a modified co-precipitation method is reported. The benefits of albumin for coating of SPIOs, i.e. its long circulation life, low immunogenicity and drug binding ability to specific binding domains, were all retained in our mildly modified BSA. The BSA-SPIOs thus prepared displayed an excellent T₂ contrast enhancing effect and drug loading capacity. Two cytotoxic drugs curcumin and sunitinib, where the former is a drug-resistance depressor and the latter is a tyrosine kinase inhibitor, were further co-loaded into the BSA-SPIOs (denoted SPIO-SC) to achieve combined synergistic therapy. SPIO-SC formulations displayed the most significant tumor inhibition yet least drug-induced toxicity both in vitro and in vivo when compared with free drug formulations. Through in vivo pharmacokinetic analysis, it was demonstrated that SPIO-SC most efficiently delivered the encapsulated drugs to the tumor site, and at the same time maintained the originally designed, optimal ratios of curcumin to sunitinib concentrations at the tumor target and yielded the most optimal synergistic effect and, subsequently, the more effective therapeutic outcomes. The prepared BSA-SPIOs are an extremely promising candidate for both MR imaging and drug delivery as a healthcare material.