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As one of the most significant imaging modalities currently available, magnetic resonance imaging (MRI) has been extensively utilized for clinically accurate cancer diagnosis. However, low signal-to-noise ratio (SNR) and low specificity for tumors continue to pose significant challenges. Inspired by the distance-dependent magnetic resonance tuning (MRET) phenomenon, the tumor microenvironment (TME)-activated off–on T1–T2 dual-mode MRI nanoswitch is presented in the current study to realize the sensitive early diagnosis of tumors. The tumor-specific nanoswitch is designed and manufactured on the basis of PDGFB-conjugating ferroferric oxide coated by Mn-doped silica (PDGFB-FMS), which can be degraded under the high-concentration GSH and low pH in TME to activate the T1–T2 dual-mode MRI signals. The tumor-specific off–on dual-mode MRI nanoswitch can significantly improve the SNR and is used successfully for the accurate diagnosis of early-stage tumors, particularly for orthotopic prostate cancer. In addition, the systemic delivery of the nanoswitch did not cause blood or tissue damage, and it can be excreted out of the body in a timely manner, demonstrating excellent biosafety. Overall, the strategy is a significant step in the direction of designing off–on dual-mode MRI nanoprobes to improve imaging accuracy, which opens up new avenues for the development of new MRI probes. [ABSTRACT FROM AUTHOR]

Iron oxide nanoparticles (IONPs)-based contrast agents are widely used for T2-weighted magnetic resonance imaging (MRI) in clinical diagnosis, highlighting the necessity and importance to evaluate their potential systematic toxicities. Although a few previous studies have documented the toxicity concerns of IONPs to major organs, limited data are available on the potential reproductive toxicity caused by IONPs, especially when administrated via intravenous injection to mimic clinical use of MRI contrast agents. Our study aimed to determine whether exposure to IONPs would affect male reproductive system and cause other related health concerns in ICR mice. The mice were intravenously injected with different concentrations IONPs once followed by routine toxicity tests of major organs and a series of reproductive function-related analyses at different timepoints. As a result, most of the contrast agents were captured by reticuloendothelial system (RES) organs such as liver and spleen, while IONPs have not presented adverse effects on the normal function of these major organs. In contrast, although IONPs were not able to enter testis through the blood testicular barrier (BTB), and they have not obviously impaired the overall testicular function or altered the serum sex hormones levels, IONPs exposure could damage Sertoli cells in BTB especially at a relative high concentration. Moreover, IONPs administration led to a short-term reduction in the quantity and quality of sperms in a dose-dependent manner, which might be attributed to the increase of oxidative stress and apoptotic activity in epididymis. However, the semen parameters have gradually returned to the normal range within 14 days after the initial injection of IONPs. Collectively, these results demonstrated that IONPs could cause reversible damage to the reproductive system of male mice without affecting the main organs, providing new guidance for the clinical application of IONPs as T2-MRI contrast agents. [ABSTRACT FROM AUTHOR]

Graphical abstract Highlights • High performance dual-mode contrast agent (GdIONC) was developed. • The nested porous structure dramatically enhanced water-interaction around GdIONC. • High specific surface area increased the number of water molecules around GdIONC. • Hydrogen bonds effectively prolonged the rotational correlation time of proton. • Oxide vacancies sharply enhanced the water residence time and exchange efficiency. Abstract Rational structure design benefits the development of new classes of contrast agents (CAs) with excellent magnetic resonance imaging performance. In this work, hydrogenated silica with a net nanostructure (HSiO 2) was fabricated and used to modify gadolinium-doped iron oxide nanoclusters (GdIONCs) to form a core-shell nanoplatform (HSiO 2 @GdIONC) with enhanced T 1 and T 2 contrast ability. In this nanoplatform, the HSiO 2 shell showed a strong binding capacity for water molecules because of the presence of hydrogen bonds, oxygen vacancies, and high specific surface areas, and the strong binding capacity significantly improved the spin-spin (T 2) and spin-lattice (T 1) imaging of the GdIONC core. In addition, the T 1 relaxation rate of the GdIONC core dramatically increased from 30.8 mM−1 s−1 to 38.2 mM−1 s−1 after being coated with the HSiO 2 shell, and the r 2 to r 1 ratio decreased from 10.9 to 8.3, which is an appropriate ratio (r 2 /r 1 : 5–10) for dual-mode contrast. Cell and animal experiments suggested that HSiO 2 @GdIONC exhibited a better T 1 - and T 2 -weighted MR imaging effect than the bare GdIONC core, confirming that this strategy for modifying GdIONCs is a beneficial and promising approach for obtaining highly efficient dual-mode CAs. [ABSTRACT FROM AUTHOR]

Abstract In this work, a tumor microenvironment (TME)-responsive biodegradable MnSiO 3 @Fe 3 O 4 nanoplatform for dual-mode magnetic resonance imaging (MRI)-guided combinatorial cancer therapy was constructed. Fe 3 O 4 nanoparticles decorated on the surface of MnSiO 3 could effectively obstruct the pores of MnSiO 3 and reduce the leakage of anticancer drugs under physiological conditions. The structure of the nanoplatform was broken under the weakly acidic and high-concentration glutathione conditions in the TME, resulting in the separation of the Fe 3 O 4 nanoparticles from the nanoplatform and rapid drug release. In addition, the exfoliated Fe 3 O 4 and released Mn2+ can help reduce the interference between their T 1 and T 2 contrast abilities, resulting in dual-mode MRI contrast enhancement. Furthermore, during the exfoliation process of the Fe 3 O 4 nanocrystals, the catalytic activity of the Fe 3 O 4 nanocrystals toward a Fenton-like reaction within cancer cells could be improved because of the increase in specific surface area, which led to the generation of highly toxic hydroxyl radicals and induced HeLa cell apoptosis. The nanoplatform also displayed excellent T 1 -T 2 dual-mode MRI contrast enhancement and anticancer activity in vivo with reduced systemic toxicity. Thus, this multifunctional nanoplatform could be a potential nanotheranostic for dual-mode MRI-guided combinatorial cancer therapy. Graphical abstract A multifunctional MnSiO 3 @Fe 3 O 4 nanoplatform is constructed by decorating Fe 3 O 4 nanoparticles on the surface of MnSiO 3 , followed by amination and grafting PEG on the surface and subsequently loading cisplatin into the nanoplatform. This well-engineered nanoplatform with tumor microenvironment-responsive biodegradable ability displays outstanding dual-mode MRI-guided combinatorial catalytic nanotherapeutics (the generation of ·OH) and chemotherapy for cancer treatment. Image 1 [ABSTRACT FROM AUTHOR]

Chemodynamic therapy (CDT) was widely exploited for cancer therapy and expected to replace traditional anticancer drug therapies. Generally, CDT needs to combine with extra therapeutic methods for obtaining the optimal therapeutic efficacy of cancer. Herein, a multifunctional theranostic platform combing CDT with limotherapy was developed via nanoselenium (nano-Se)-coated manganese carbonate-deposited iron oxide nanoparticle (MCDION-Se). MCDION-Se could release abundant of Mn2+ ions that catalyzed H 2 O 2 into hydroxyl radicals (· OH) via a Fenton-like reaction, effectively inducing the apoptosis of cancer cells. Besides, nano-Se coated onto MCDION-Se also dramatically activated superoxide dismutase (SOD) and promoted the generation of superoxide anion radicals (SOARs) in tumor tissue. Subsequently, a high content of H 2 O 2 was produced via SOD catalysis of SOARs, further enhancing CDT efficiency. Meanwhile, the nano-Se and Mn2+ ions inhibited the generation of adenosine triphosphate (ATP), thus starving cancer cells. In addition, in vitro and in vivo experiments showed that MCDION-Se could effectively enhance the contrast of tumor tissue and improve the quality of magnetic resonance imaging (MRI). Overall, this work provided a nanoplatform that combined CDT with limotherapy for cancer therapy and simultaneously utilized MRI for monitoring the treatment of tumors. A pH-responsive free-drug theranostic platform (MCDION-Se) combined chemodynamic therapy with limotherapy was developed for MRI-guided tumor therapy. Image 1 [ABSTRACT FROM AUTHOR]

[Display omitted] • A series of atomically precise Gd-doped MMIONs (Gd x Fe 3−x O 4 nanoclusters) was fabricated. • Gd doping could effectively regulate the magnetic properties, size and morphology of Gd x Fe 3−x O 4. • The Gd content of Gd x Fe 3−x O 4 was optimized, then the optimal T 2 contrast performance was achieved. • The Gd x Fe 3−x O 4 nanocluster showed favorable bio-safety in vitro and in vivo. The use of multi-domain magnetic iron oxide nanoclusters (MMIONs) as Magnetic resonance imaging (MRI) contrast agent is facing problems of strong ferromagnetism and thus weak T 2 contrast ability. The doping of Gd ions holds potential to solve these problems by reducing ferromagnetism and enhancing transverse relaxivity (r 2), but the exact role of doping in modulating the contrast properties remain unknown. Herein, we prepared a series of atomically precise Gd x Fe 3−x O 4 nanoclusters and systematically explored the effect of Gd doping on tuning their morphology, magnetic property, and r 2 value. After the doping of Gd ions, the specific surface area of Gd x Fe 3−x O 4 nanoclusters significantly increased, and meanwhile, the magnetic property of Gd x Fe 3-x O 4 nanoclusters transformed from ferromagnetism to superparamagnetism, which led to stronger T 2 contrast. Specifically, the highest r 2 value was obtained at 488 mM−1s−1 (7.0 T) for Gd 0.072 Fe 2.928 O 4 nanocluster, four times higher than that for pristine Fe 3 O 4 (110 mM−1s−1). For potential applications, we validated the outstanding contrast of Gd 0.018 Fe 2.982 O 4 nanocluster (r 2 = 481 mM−1s−1 at 7.0 T) to diagnose early orthotopic cancer in mice. This work opens up a new avenue for the development of atomically precise Gd-doped MMIONs as efficient T 2 -weighted MRI contrast agents. [ABSTRACT FROM AUTHOR]