Drug delivery is a key component of nanomedicine, and conventional delivery relies on the adsorption or encapsulation of drug molecules to a nanomaterial. Many delivery vehicles contain metal ions, such as metal–organic frameworks, metal oxides, transition metal dichalcogenides, MXene, and noble metal nanoparticles. These materials have a high metal content and pose potential long‐term toxicity concerns leading to difficulties for clinical approval. In this review, recent developments are summarized in the use of drug molecules as ligands for metal coordination forming various nanomaterials and soft materials. In these cases, the drug‐to‐metal ratio is much higher than conventional adsorption‐based strategies. The drug molecules are divided into small‐molecule drugs, nucleic acids, and proteins. The formed hybrid materials mainly include nanoparticles and hydrogels, upon which targeting ligands can be grafted to improve efficacy and further decrease toxicity. The application of these materials for addressing cancer, viral infection, bacterial infection inflammatory bowel disease, and bone diseases is reviewed. In the end, some future directions are discussed from fundamental research, materials science, and medicine.

Bladder cancer remains one of the most common malignant tumors that threatens human health worldwide. It imposes a heavy burden on patients and society due to the high medical costs associated with its easy metastasis and recurrence. Although several treatment options for bladder cancer are available, their clinical efficacy remains unsatisfactory. Therefore, actively exploring new drugs and their mechanisms of action for the clinical treatment of bladder cancer is very important. Scabertopin is one of the major sesquiterpene lactones found in Elephantopus scaber L. Sesquiterpene lactones are thought to have fairly strong anti-cancer efficacy. However, the anticancer effect of sesquiterpenoid scabertopin on bladder cancer and its mechanism are still unclear. The aim of this study is to evaluate the antitumor activity of scabertopin in bladder cancer and its potential molecular mechanism in vitro. Our results suggest that scabertopin can induce RIP1/RIP3-dependent necroptosis in bladder cancer cells by promoting the production of mitochondrial reactive oxygen species (ROS), inhibit the expression of MMP-9 by inhibiting the FAK/PI3K/Akt signaling pathway, and ultimately inhibit the migration and invasion ability of bladder cancer cells. At the same time, we also demonstrated that the half-inhibition concentration (IC50) of scabertopin on various bladder cancer cell lines (J82, T24, RT4 and 5637) is much lower than that on human ureteral epithelial immortalized cells (SV-HUC-1). The above observations indicate that scabertopin is a potential therapeutic agent for bladder cancer that acts by inducing necroptosis and inhibiting metastasis.

RNA-binding proteins (RBPs) are key regulators of transcription and translation, with highly dynamic spatio-temporal regulation. They are usually involved in the regulation of RNA splicing, polyadenylation, and mRNA stability and mediate processes such as mRNA localization and translation, thereby affecting the RNA life cycle and causing the production of abnormal protein phenotypes that lead to tumorigenesis and development. Accumulating evidence supports that RBPs play critical roles in vital life processes, such as bladder cancer initiation, progression, metastasis, and drug resistance. Uncovering the regulatory mechanisms of RBPs in bladder cancer is aimed at addressing the occurrence and progression of bladder cancer and finding new therapies for cancer treatment. This article reviews the effects and mechanisms of several RBPs on bladder cancer and summarizes the different types of RBPs involved in the progression of bladder cancer and the potential molecular mechanisms by which they are regulated, with a view to providing information for basic and clinical researchers.

Immunotherapy resistance in bladder cancer (BLCA) is associated with elevated levels of sialic acid–binding immunoglobulin-like lectin (Siglec15). This protein plays a crucial role in fostering a noninflammatory tumor microenvironment (TME), which is conducive to cancer progression. Our study confirmed that the overexpression of Siglec15 led to a reduction in CD8+ T cell infiltration. This effect was mediated by the downregulation of pro-inflammatory cytokines and chemokines, which in turn exacerbated BLCA malignancy. Furthermore, Siglec15 inhibited the cytotoxicity of effector T cell, contributing to immune evasion. An in vivo study demonstrated that Siglec15 overexpression induced a non-inflammatory TME and promoted resistance to immunotherapy. These findings highlight Siglec15 as a potential therapeutic target for BLCA. By modulating inflammation in the TME and CD8+ T cell function, targeting Siglec15 may offer a novel strategy for overcoming immunotherapy resistance and improving patient outcomes.

Non-muscle-invasive bladder cancer (NMIBC) is a common tumor of the urinary system. Given its high rates of recurrence, progression, and drug resistance, NMIBC seriously affects the quality of life and limits the survival time of patients. Pirarubicin (THP) is a bladder infusion chemotherapy drug recommended by the guidelines for NMIBC. Although the widespread use of THP reduces the recurrence rate of NMIBC, 10–50% of patients still suffer from tumor recurrence, which is closely related to tumor resistance to chemotherapy drugs. This study was performed to screen the critical genes causing THP resistance in bladder cancer cell lines by using the CRISPR/dCas9-SAM system. Thus, AKR1C1 was screened. Results showed that the high expression of AKR1C1 could enhance the drug resistance of bladder cancer to THP both in vivo and in vitro. This gene could reduce the levels of 4-hydroxynonenal and reactive oxygen species (ROS) and resist THP-induced apoptosis. However, AKR1C1 did not affect the proliferation, invasion, or migration of the bladder cancer cells. Aspirin, which is an AKR1C1 inhibitor, could help reduce the drug resistance caused by AKR1C1. After receiving THP treatment, the bladder cancer cell lines could upregulate the expression of the AKR1C1 gene through the ROS/KEAP1/NRF2 pathway, leading to resistance to THP treatment. Using tempol, which is an inhibitor of ROS, could prevent the upregulation of AKR1C1 expression.