ABSTRACT
The combination of anti-rheumatoid arthritis (RA) drugs methotrexate (MTX) and baricitinib (BTN) has been reported to improve RA treatment efficacy. However, study on the strategy of combination is elusive when considering the benefit of the synergy between MTX and BTN. In this study, we found that the N-heterocyclic rings in the MTX and BTN offer hydrogen bonds and π-π stacking interactions, driving the formation of exquisite vesicular morphology of nanovesicles, denoted as MB NVs. The MB NVs with the MTX/BTN weight ratio of 2:1, MB NVs (2:1), showed an improved anti-RA effect through the synergy between the anti-inflammatory and antiproliferative responses. This work presents that the intermolecular interactions between drug molecules could mediate the coassembly behavior into nanomedicine as well as the therapy synergy both in vitro and in vivo, which may provide further understanding on the rational design of combination nanomedicine for therapeutic purposes.
Subject(s)
Antirheumatic Agents , Arthritis, Rheumatoid , Azetidines , Purines , Pyrazoles , Sulfonamides , Humans , Methotrexate/pharmacology , Methotrexate/therapeutic use , Antirheumatic Agents/pharmacology , Antirheumatic Agents/therapeutic use , Nanomedicine , Arthritis, Rheumatoid/drug therapy , Treatment Outcome , Drug Therapy, CombinationABSTRACT
Macrophages play a crucial role in immune activation and provide great value in the prognosis of cancer treatments. Current strategies for prognostic evaluation of macrophages mainly target the specific biomarkers to reveal the number and distribution of macrophages in the tumors, whereas the phenotypic change of M1 and M2 macrophages in situ is less understood. Here, we designed an ultrasmall superparamagnetic iron oxide nanoparticle-based molecular imaging nanoprobe to quantify the repolarization of M2 to M1 macrophages by magnetic resonance imaging (MRI) using the redox-active nitric oxide (NO) as a vivid chemical target. The nanoprobe equipped with O-phenylenediamine groups could react with the intracellular NO molecules during the repolarization of M2 macrophages to the M1 phenotype, leading to electrical attraction and colloidal aggregation of the nanoprobes. Consequently, the prominent changes of the T1 and T2 relaxation in MRI allow for the quantification of the macrophage polarization. In a 4T1 breast cancer model, the MRI nanoprobe was able to reveal macrophage polarization and predict treatment efficiency in both immunotherapy and radiotherapy paradigms. This study presents a noninvasive approach to monitor the phenotypic changes of M2 to M1 macrophages in the tumors, providing insight into the prognostic evaluation of cancer treatments regarding macrophage-mediated immune responses.
Subject(s)
Neoplasms , Nitric Oxide , Humans , Macrophages , Prognosis , Neoplasms/diagnostic imaging , Neoplasms/therapy , Neoplasms/pathology , Magnetic Resonance ImagingABSTRACT
The pathogenesis of various diseases often involves an intricate interplay between membrane proteins and membrane curvature. Understanding the underlying mechanisms of this interaction could offer novel perspectives on disease treatment. In this review, we provide an introduction to membrane curvature and its association with membrane proteins. Furthermore, we delve into the impact and potential implications of this interaction in the context of disease treatment. Lastly, we discuss the prospects and challenges associated with harnessing these interactions for effective disease management, aiming to provide fresh insights into therapeutic strategies.
