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Metabolism is a fundamental process that underlies human health and diseases. Nuclear magnetic resonance (NMR) techniques offer a powerful approach to identify metabolic processes and track the flux of metabolites at the molecular level in living systems. An in vitro study through in-cell NMR tracks metabolites in real time and investigates protein structures and dynamics in a state close to their most natural environment. This technique characterizes metabolites and proteins involved in metabolic pathways in prokaryotic and eukaryotic cells. In vivo magnetic resonance spectroscopy (MRS) enables whole-organism metabolic monitoring by visualizing the spatial distribution of metabolites and targeted proteins. One limitation of these NMR techniques is the sensitivity, for which a possible improved approach is through isotopic enrichment or hyperpolarization methods, including dynamic nuclear polarization (DNP) and parahydrogen-induced polarization (PHIP). DNP involves the transfer of high polarization from electronic spins of radicals to surrounding nuclear spins for signal enhancements, allowing the detection of low-abundance metabolites and real-time monitoring of metabolic activities. PHIP enables the transfer of nuclear spin polarization from parahydrogen to other nuclei for signal enhancements, particularly in proton NMR, and has been applied in studies of enzymatic reactions and cell signaling. This review provides an overview of in-cell NMR, in vivo MRS, and hyperpolarization techniques, highlighting their applications in metabolic studies and discussing challenges and future perspectives., (© 2024. The Author(s).)

Background: The 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 T 1 - and T 2 -weighted MRI functions, and thereby realizing imaging guided drug delivery and targeted therapy., Results: Theranostic nanocomposites Mn-porphyrin&Fe 3 O 4 @SiO 2 @PAA-cRGD were fabricated and characterized, and the nanocomposites were effectively used in T 1 - and T 2 -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 r 2 /r 1 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 T 1 /T 2 dual-mode contrast agent at acidic environments of tumor. For in vivo MRI, T 1 and T 2 relaxation was significantly accelerated to 55 and 37%, respectively, in the tumor after i.v. injection of nanocomposites., Conclusion: The 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.

Liposomes are effective drug delivery systems that can be functionalized with imaging contrast agents, providing both diagnosis and monitoring of disease treatment. Here we describe the design of a theranostic liposomal drug delivery system whose biodistribution can be real time imaged by contrast enhanced MRI and can achieve tandem chemotherapy drug delivery. Because T1 relaxation of MRI depends upon the chemical structure of contrast agent as well as its interaction with neighbor environment, we rationally designed a functional liposome for in vivo T1 enhanced MRI. The liposome shows a 36-fold higher T1 relaxation rate over the commercial MRI contrast agent Omniscan® and a long circulation time up to 300min in vivo. Moreover, the multifunctional liposome carries both hydrophobic and hydrophilic chemotherapeutic drugs, can synergistically enhance therapeutic effects of multiple drugs and selectively deliver them to lung tumors, leading to lower doses, toxicity and sustained release. The nanoparticles, which exhibit favorable biodistributions to tumors, offer new possibilities for the simultaneous delivery of more than one drug and the evaluation of therapeutic response in vivo by T1 enhanced MRI., Statement of Significance: Cancer cells invoke different mechanisms to resist cancer therapies, particularly when delivering a single agent in a given therapy. The combination of two (or more) thermotherapy agents provides a promising way to circumvent such situations of drug resistance, due to a favorable synergistic effect that "tricks" the drug resistance mechanism. However, challenges to the simultaneous delivery of two drugs prevail, especially with regards to the simultaneous delivery of hydrophobic and hydrophobic drugs. Furthermore, non-invasive in vivo imaging of drug distribution enables the real-time monitoring and prediction of therapeutic responses to treatment. In this study, we rationally designed a theranostic liposomal drug delivery system whose biodistribution can be imaged via T1-weighted MRI in real-time and can achieve tandem chemotherapy drug delivery. This original study will be of considerable use to the wider drug delivery community., (Copyright © 2016 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.)