A theranostic nanocomposite system based on radial mesoporous silica hybridized with Fe3O4 nanoparticles for targeted magnetic field responsive chemotherapy of breast cancer

摘要

Achieving accumulation of a target drug in tumor tissue, optimal release behavior and concurrent diagnostic imaging with therapy (theranostic) requires an ideal chemotherapy protocol that involves the responsive control of drug delivery. In the current study, we report the construction of a novel theranostic drug delivery system based on radial mesoporous silica, which is hybridized with multiscale magnetic nanoparticles for MRI-guided and alternative magnetic field (AMF) responsive chemotherapy for breast cancer. Superparamagnetic iron oxide nanoparticles (IONPs) with multiscale sizes were prepared via a hydrothermal method (for larger IONPs, lIO NPs) and a thermal decomposition method (for ultra-small IONPs, uIO NPs). lIO NPs act as the heat mediator that is responsive to the AMF, while uIO NPs act as the T-2 contrast agent for MRI. Mesoporous silica nanoparticles with radially oriented mesochannels were further in situ grown onto the surfaces of the lIO NPs, and both the uIO NPs and doxorubicin, an anti-cancer drug, can be readily incorporated within the mesochannels. To endow the as-prepared doxorubicin-loaded nano-hybrids with a good targeting ability, the surfaces of the particles were modified with folic acid (FA). This prepared drug delivery system based on magnetic/silica nanocomposites showed high drug loading efficiency and AMF stimuli responsive release properties. Meanwhile, in vitro MRI measurements revealed an excellent MRI contrast effect with a high relaxation value of 308 mM(-1) s(-1). Furthermore, both in vitro cytotoxicity analysis and in vivo anti-tumor effect evaluation demonstrated that the drug delivery system possesses great potential as an MRI-guided stimuli-responsive theranostic platform for effective active targeting chemotherapy of cancer.