pH-responsive theranostic nanocomposites as synergistically enhancing positive and negative magnetic resonance imaging contrast agents

Abstract

BackgroundThe rational design of theranostic nanoprobe to present responsive effect of therapeutic potency and enhanced diagnostic imaging in tumor milieu plays a vital role for efficient personalized cancer therapy and other biomedical applications. We aimed to afford a potential strategy to pose both T1- and T2-weighted MRI functions, and thereby realizing imaging guided drug delivery and targeted therapy.ResultsTheranostic nanocomposites Mn-porphyrin&Fe3O4@SiO2@PAA-cRGD were fabricated and characterized, and the nanocomposites were effectively used in T1- and T2-weighted MRI and pH-responsive drug release. Fluorescent imaging also showed that the nanocomposites specifically accumulated in lung cancer cells by a receptor-mediated process, and were nontoxic to normal cells. The r2/r1 ratio was 20.6 in neutral pH 7.4, which decreased to 7.7 in acidic pH 5.0, suggesting the NCs could act as an ideal T1/T2 dual-mode contrast agent at acidic environments of tumor. For in vivo MRI, T1 and T2 relaxation was significantly accelerated to 55 and 37%, respectively, in the tumor after i.v. injection of nanocomposites.ConclusionThe synthesized nanocomposites exhibited highly sensitive MRI contrast function no matter in solution, cells or in vivo by synergistically enhancing positive and negative magnetic resonance imaging signals. The nanocomposites showed great potential for integrating imaging diagnosis and drug controlled release into one composition and providing real-time imaging with greatly enhanced diagnostic accuracy during targeted therapy. Electronic supplementary materialThe online version of this article (10.1186/s12951-018-0350-5) contains supplementary material, which is available to authorized users.

Recent Progress on Manganese‐Based Nanostructures as Responsive MRI Contrast Agents

“…This increased hydration enhances the interactions between Mn 2+ and water, leading to a decrease of the relaxation time. Another example of this approach comes from Huang et al., who prepared magnetic nanoparticles coated with two layers of silica (solid and mesoporous) and functionalized with PAA. At neutral pH, these particles were negatively charged thanks to the large number of carboxylic groups from the polymer.…”

Synthesis of a Thermal‐Responsive Dual‐Modal Supramolecular Probe for Magnetic Resonance Imaging and Fluorescence Imaging

“…MRI/FI dual‐modality probes combine the excellent spatial resolution of MRI with the high sensitivity of FI. [ 19–24 ]…”

Recent Advances of Manganese-Based Hybrid Nanomaterials for Cancer Precision Medicine

“…Owing to superb soft tissue imaging contrast, high spatial resolution, multidimensional imaging, and absence of ionizing radiation, MRI becomes increasingly available for early detection of tumors with gadolinium (Gd)-based contrast agents (CAs) most frequently used (9,10). Unfortunately, Gdbased CA is in restricted use by the Food and Drug Administration (FDA) due to possibly Gd-based CA-linked medical conditions known as nephrogenic systemic fibrosis (NSF), chronic kidney disease (CKD), and severe complexities, which led to new concerns on the safety of Gd as MRI CAs clinically (11)(12)(13)(14).…”