A novel intratumoral pH/redox-dual-responsive nanoplatform for cancer MR imaging and therapy

Abstract

The integration of diagnostic and therapeutic functions in a nanoplatform has been a rapidly emerging method in the management of cancer. The application of imaging technology paves the way to track the pharmacokinetics of the nanoplatforms, to guide the treatment, and to monitor the therapeutic processes and outcomes. Herein, we reported a novel type of monodisperses mesoporous silica-coated superparamagnetic iron oxide-based multifunctional nanoplatform (DOX@MMSN-SS-PEI-cit) for the diagnosis and treatment of cancer. The fabrication process included the surface modification of monodisperses mesoporous silica nanoparticle (MMSN) with branched polyethyleneimine (PEI) via disulfide bonds and the further coupling of citraconic anhydride to PEI. Typically, the hydrolysis of amide bonds in the tumor microenvironment (TME) could lead to a negative-to-positive charge reversion, which can enhance the endosomal escape of the resulting nanoplatform. The rapid release of doxorubicin hydrochloride (DOX) directly killed the cancer cells. Due to the superparamagnetic iron oxide-based high-resolution T₂-weighted MR imaging contrast agents, this novel multifunctional nanoplatform successfully realized MR imaging, targeted drug delivery and controlled release in one system, and achieved significant improvement in tumor diagnosis and therapy. In summary, the therapeutic nanoplatform is a promising option in precise cancer treatment.

Keywords: Cancer theranostics; Charge-reversal; Controlled release; Magnetic resonance imaging; pH/redox-dual-responsive.