Composition–property relationships in multifunctional hollow mesoporous carbon nanosystems for PH-responsive magnetic resonance imaging and on-demand drug release

Abstract

The construction of intelligent stimuli-responsive nanosystems can substantially improve the sensitivity/resolution/specificity of diagnostic imaging and enhance the therapeutic efficiency of chemotherapy for cancer treatment. This work reports on a generic construction strategy to achieve a multiple stimuli-responsive theranostic system for cancer simply by optimizing the chemical compositions of inorganic nanoplatforms to avoid the tedious and complicated synthetic procedure for traditional organic or organic/inorganic nanosystems. Based on the “breaking up” nature of manganese oxides and specific features of the carbonaceous framework to interact with aromatic drug molecules, manganese oxide nanoparticles were elaborately integrated into hollow mesoporous carbon nanocapsules by a simple in situ framework redox strategy to realize concurrent pH-sensitive T₁-weighted magnetic resonance imaging (MRI) and pH-/HIFU-responsive on-demand drug release. The ultrasensitive disease-triggered MRI performance has been successfully demonstrated by a 52.5-fold increase of longitudinal relaxivity (r₁ = 10.5 mM⁻¹ s⁻¹) and on nude mice 4T1 xenograft. The pH- and HIFU-triggered doxorubicin release and enhanced therapeutic outcome against multidrug resistance of cancer cells were systematically confirmed. In particular, the fabricated inorganic composite nanocapsules were found to feature unique biological behaviours, such as antimetastasis effect, extremely low hemolysis against red blood cells and high in vivo histocompatibility. This report on the successful construction of a pure inorganic nanosystem with multiple stimuli-responsivenesses may pave the way to new methods for the development of intelligent nanofamilies for cancer therapy.