Chenglong Li

Objective: To explore the current status of therapeutic drug monitoring (TDM) research on anticancer drugs, analyze research hotspots and trends, and provide insights and references for future studies. Methods: Data were retrieved from the Web of Science Core Collection (1990–2024) using keywords related to “anticancer drugs” and “therapeutic drug monitoring.” Bibliometric analyses were performed using VOSviewer, CiteSpace, R, and Scimago Graphica to visualize trends in publications, keywords, collaborations, and citation networks. Results: A total of 1474 articles were included. Global research output on TDM for anticancer drugs has grown steadily, with an accelerating trend in recent years. Key research themes include drug-specific monitoring, analytical methodologies, and clinical safety and efficacy. Busulfan remains the most studied agent in hematologic malignancies, while tyrosine kinase inhibitors, particularly crizotinib and nilotinib, along with monoclonal antibodies, have emerged as focal points of recent citation bursts. The keyword “pediatric patients” also shows a strong burst signal, reflecting growing attention to developmental pharmacokinetics and individualized dosing in vulnerable populations. The majority of influential studies were published in clinical oncology and pharmacology journals, with chemotherapy and targeted therapy dominating among the most cited papers. The United States, China, Japan, and Western European countries, notably the Netherlands and France, account for the majority of global publications. Among these, the Netherlands, Switzerland, and France demonstrate not only the highest research intensity, as measured by the Relative Importance Index (RII), but also a gradual increase in RII over time. Institutional-level RII analysis further highlights sustained contributions from leading European academic and clinical networks. International collaboration is highly concentrated among these high-output regions, forming a tightly interconnected research network. Conclusion: This study maps the evolving landscape of TDM in oncology. Accelerating research on tyrosine kinase inhibitors, monoclonal antibodies, and pediatric populations highlights TDM’s clinical value in optimizing therapy for narrow-therapeutic-index drugs. Rising research intensity in Europe and strong international collaboration underscore a coordinated global effort, supporting TDM’s integration into precision oncology, especially for vulnerable patients.

Copper deficiency, commonly observed in myocardial infarction, leads to cardiomyocyte loss and cardiac dysfunction, yet the mechanism driving copper efflux remains unclear. To further elucidate the relationship between copper transporters and cardiac copper efflux during chronic myocardial ischemia, a rhesus monkey model was established by performing the permanent ligation of the left anterior descending coronary artery. A dramatic decrease in copper concentration within ischemic cardiomyocytes was observed alongside declining cardiac function. Among major copper transporters, COMMD1 and ATP7B were significantly upregulated in the ischemic myocardium. COMMD1 was specifically localised in cardiomyocytes undergoing copper efflux, whereas increased ATP7B was restricted to cardiac fibroblasts. This indicates that elevated COMMD1 regulates copper efflux in cardiomyocytes during chronic myocardial ischemia, functioning independently of its interactions with P‐type ATPase transporters. Given the discrepancy between RNA and protein levels of COMMD1 in ischemic myocardium, post‐translational modification is likely responsible for regulating COMMD1 expression. We found that the copper‐binding protein with E3 ubiquitin ligase activity, XIAP, augmented before the rise in COMMD1 expression within ischemic cardiomyocytes. Excessive XIAP specifically interacted with COMMD1 to enhance its protein levels under copper‐deprivation conditions and vice versa. Overall, our findings reveal a positive feedback loop among XIAP, COMMD1 and copper, highlighting the intricate interplay between XIAP and COMMD1 in regulating copper efflux in cardiomyocytes. This loop sets the stage for further investigation into therapeutic strategies to manage copper homeostasis in chronic myocardial ischemia.

Background: Rheumatoid arthritis (RA) is a systemic autoimmune disease (AD), and the global incidence rate is 0.5 ~ 1%. Existing medications might reduce symptoms, however, there is no known cure for this illness. Etanercept (EN) can competitively inhibit TNF-α binding to the TNF receptor on the cell surface to treat RA. However, subcutaneous injection of free EN predisposes to systemic distribution and induces immune system hypofunction. Draining lymph nodes (LNs) play a significant role in the onset, maintenance, and progression of RA as they are the primary sites of aberrant immune response and inflammatory cytokine production. Aim: The purpose of this study was to successfully treat RA with etanercept by encapsulating it in nanoemulsions (NEs/EN) and then delivering it specifically to draining LNs. The EN-loaded NEs were prepared by high-pressure homogenization method and modified with DSPE-mPEG2000 and Ca(OH)2. Methods: A novel nano-emulsion (NE) was constructed to deliver EN (NE/EN) to RA-draining LNs. To decrease aggregation and load EN, DSPE-mPEG2000 and Ca(OH)2 were successively decorated on the surface of the lipid injectable emulsions. The hydrodynamic diameter and morphology of NEs/EN were investigated by using a laser particle size analyzer and transmission electron microscopy, respectively. The in vivo fluorescence imaging system was used to study the in vivo LN targeting ability of the formulation. In the therapeutic experiment, NEs/EN was subcutaneously administrated to inhibit the development of the mouse arthritis model. Results: Circular dichroism spectrum and L929 cell experiment confirmed that NEs encapsulation had no impact on the biological activity of EN. In vivo investigation on collagen-induced arthritis (CIA) mouse model showed that NEs/EN have good inguinal lymph node targeting capabilities, as well as, anti-inflammatory effect against RA. Compared with the free group, the paw thickness and arthritic score in NEs/EN group were significantly alleviated. Moreover, the concentration of pro-inflammatory cytokines TNF-α and IL-1β in NEs/EN-treated mice was lower than that in free EN. Conclusion: NEs/EN effectively improve the effectiveness of EN in the treatment of RA. Our work provides an experimental foundation for expanding the clinical application of EN.

Rheumatoid arthritis (RA) is a chronic autoimmune inflammation. Excessive proliferation and inadequate apoptosis of synovial macrophages are the crucial events of RA. Therefore, delivering therapeutic molecules to synovial macrophages specifically to tackle apoptotic insufficiency probably be an efficient way to reduce joint inflammation and bone erosion. Based on the characteristics of dextran sulfate (DS) specifically binding scavenger receptor A (SR-A) on macrophage and celastrol (CLT) inducing apoptosis, we designed synovial macrophage-targeted nano-emulsions encapsulated with CLT (SR-CLTNEs) and explored their anti-RA effect. After intravenous injection, fluorescence-labeled SR-CLTNEs successfully targeted inflammatory joints and synovial macrophages in a mouse model of RA, with the macrophage targeting efficiency of SR-CLTNEs, CLTNEs, and Free DID was 20.53%, 13.93%, and 9.8%, respectively. In vivo and in vitro studies showed that SR-CLTNEs effectively promoted the apoptosis of macrophages, reshaped the balance between apoptosis and proliferation, and ultimately treated RA in a high efficiency and low toxicity manner. Overall, our work demonstrates the efficacy of using SR-CLTNEs as a novel nanotherapeutic approach for RA therapy and the great translational potential of SR-CLTNEs.

Rheumatoid arthritis (RA) is a common autoimmune and inflammatory disease. Activated macrophages in arthritic joints play a prominent role in the initiation and persistence of RA. Despite great progress in the clinical treatment of RA, poor response and high discontinuation due to systemic toxicity remain unsolved issues, especially the well-known methotrexate (MTX). Therefore, active targeted delivery of therapeutic drugs to pathogenic cells in arthritic joints is essential to increase in situ activity and decrease systemic toxicity. Here, we developed an MTX-loaded macrophage-targeted nano-emulsion (NE) based on the over-expression of folate receptor (FR) on activated macrophages, the inherent high affinity of FR for folate (FA), as well as the property of MTX and phospholipids to form complexes (MTX@PC). Intravenous injection of DID-labeled MTX@PC-FA NEs into adjuvant-induced arthritis (AIA) mice, in vivo images and flow cytometry results revealed that the NEs were highly targeted to inflamed joints and macrophages, respectively. Therapeutic studies suggested that this strategy was conducive to achieve high efficacy and low toxicity of MTX in the treatment of RA. Our research highlights MTX@PC-FA NEs as a potential treatment option for RA targeting the FR-expressed activated macrophages.

Rheumatoid arthritis (RA) is a systemic autoimmune disease (AD) caused by the aberrant attack of the immune system on its own joint tissues. Genetic and environmental factors are the main reasons of immune system impairment and high incidence of RA. Although there are medications on the market that lessen disease activity, there is no known cure for RA, and patients are at risk in varying degrees of systemic immunosuppression. By transporting (encapsulating or surface binding) RA-related self-antigens, nucleic acids, immunomodulators, or cytokines, tolerogenic nanoparticles—also known as immunomodulatory nano-preparations—have the potential to gently regulate local immune responses and ultimately induce antigen-specific immune tolerance. We review the recent advances in immunomodulatory nano-preparations for delivering self-antigen or self-antigen plus immunomodulator, simulating apoptotic cell avatars in vivo, acting as artificial antigen-presenting cells, and based on scaffolds and gels, to provide a reference for developing new immunotherapies for RA.