The development of microenvironment-responsive nanoprobes has shown great promise for use in magnetic resonance imaging (MRI), with the advantage of significantly improved specificity and good biocompatibility. However, the clinical application of responsive probes is hampered by a lack of biological sensitivity for early molecular diagnostics and visualizing microenvionment of metabolism reprogramming in tumor progression. Here, we report on a dual-ratiometric magnetic resonance tunable (DMRT) nanoprobe designed by crosslinking different ratios of transferrin chelating gadolinium and superparamagnetic nanoparticles, complexed to a pH responsive biocompatible polymer. This dually activatable nanoprobe enables pH-dependent tumor microenvironment visualization, providing exceptional quantitative pathophysiological information in vitro and in vivo. When used in combination with dual-contrast enhancement triple subtraction imaging technique (DETSI), this smart nanoprobe guarantees the diagnosis of early-stage diseases. We envisage that this novel integrated nanoplatform will provide a new paradigm for the clinical translation of robust DMRT nanoprobes for early disease detection and staging, as well as microenvironment visualization and disease progression monitoring.

Construction of micro tumor sensitive theranostic nanoagents that can increase the accuracy of imaging diagnosis and boost the therapeutic efficacy has been demonstrated for a promising approach for diagnosis and treatment of cancer. Herein, we reported a novel super-paramagnetic iron oxide (SPIO) based nanoplatform that possess significantly enhanced magnetic resonance property and photothermal effect for tumor theranostic purpose. This polyethylene glycol with four phenylboronic acid (PEG-B4)/CNTs@porphyrin (ph)/SPIO (BCPS) nanoplatform was simply prepared via integrated SPIO, ph, and a novel dendrimer with PEG liner and four PBA groups (PEG-B4) on the surface of carbon nanotubes (CNTs). Subsequently, a significant T2 relaxation rate enhanced can be achieved by the reduced accessibility of water to SPIO clustering. Moreover, the synergetic enhanced photothermal from BCPS nanoplatform contributed to better photothermal effect for cancer therapy. Furthermore, the targeting ability to sialic acid overexpressed tumor was further introduced from phenylboronic acid from PEG-B4. We showed that BCPS nanoplatform could not only selectively identify solid tumors and detect micro-sized metastatic tumor (1 mm) in the liver, but also effectively ablate tumors in a xenograft model, thereby achieving a complete cure rate of 100% at low laser dose. Our results highlight the potential of BCPS nanoplatform for accurate micro-tumor diagnosis and effective tumor therapy.