Clusterin (CLU) is a heterodimeric glycoprotein that has been detected in diverse human tissues and implicated in many cellular processes. Accumulating evidence indicates that the expression of secreted CLU correlates with the progression of cancers. However, the molecular mechanisms underlying its tumor-suppressive roles are incompletely uncovered. In this study, we demonstrate that precursor CLU is widely downregulated in lung cancer tissue, in which secretory CLU proteins are slightly decreased. Impressively, overexpressing CLU potently inhibits the migration, invasion and metastasis of lung cancer cells, whereas silencing CLU promotes this behavior; however, it appears that secretory CLU fails to exert similar anti-metastatic effects. Interestingly, the cytoplasmic precursor CLU binds ROCK1 to abrogate the interaction between ROCK1 and ERK and impair ERK activity, leading to the suppression of lung cancer invasiveness. Meanwhile, the expression of CLU was remarkably diminished in lung cancer bone metastasis loci when compared with subcutaneous tumors in the mouse model and hardly detected in the bone metastasis loci of lung cancer patients when compared with the primary. These findings reveal a novel insight into the function and regulation of cytoplasmic CLU in lung cancer, which might be a potential target for the diagnosis and treatment of metastatic lung cancer.

The genetic manipulation of Mycobacterium tuberculosis genome is limited by the availability of selection markers. Spontaneous resistance mutation rate of M. tuberculosis to the widely used kanamycin is relatively high which often leads to some false positive transformants. Due to the few available markers, we have created a cassette containing thiostrepton resistance gene (tsr) for selection in M. tuberculosis and M. bovis BCG, and gentamicin resistance gene (aacC1) for Escherichia coli and M. smegmatis mc²155, flanked with dif sequences recognized by the Xer system of mycobacteria. This cassette adds to the limited available selection markers for mycobacteria.

Midnolin (MIDN) is a protein coding gene that promotes the destruction of transcription factors encoded by immediate‐early genes. Previous research has found that those immediate‐early genes are involved in tumour progression. However, the role of MIDN is still not clearly identified in human cancers. With the help of the TCGA, GTEx, and HPA databases, we revealed that the expression of MIDN was disordered in cancers. MIDN is a potential prognostic biomarker in liver cancer and bladder cancer. Prognostic analysis indicates that the expression level of MIDN gains survival benefits or promotes progression in multiple tumours. After analysing the sequencing results of TCGA via Gene Set Enrichment Analysis (GSEA), results suggested the regulative role of MIDN in cell proliferation and tumour immunity. Single cell sequencing results revealed that MIDN is highly expressed in several tumour tissues and also expressed in immune cells. With the help of the ESTIMATE, TIMER, and CIBERSORT databases, we analysed the immune score, immune cell infiltration, and anti‐cancer immunity cycle depending on the expression of MIDN. Results showed that low MIDN levels are tightly associated with high CD4 + T and NK cell infiltration. Furthermore, mutations of MIDN in cancers were significantly associated with immune cell infiltration. This study presents a robust link between the expression of MIDN and tumour progression across multiple cancer types. The MIDN/CTNNB1/MMP9 axis promotes liver cancer progression via inducing a suppressive tumour immune microenvironment.

Conventional radiotherapy compromises antitumor immunity through collateral damage to immune cells. While boron neutron capture therapy (BNCT) enables tumor-selective ¹⁰B (n, α) ⁷Li reactions, clinical agents like boronophenylalanine (BPA) suffer from excessive dosing and exhibit immune-metabolic inertia. We report a biomineralized albumin-based BNCT agent (Albumin@MnB) synthesized from clinically accessible borax, manganese, and albumin, which unlocks neutron capture-triggered immunotherapeutic activation. Albumin@MnB achieves potent tumor suppression at reduced boron doses, demonstrating superior efficacy compared with BPA. Importantly, Albumin@MnB enhances intratumoral immune cell infiltration and suppresses distant tumor growth, synergizing with adoptive T cell immunotherapy and immune checkpoint inhibitors. By integrating tumor-specific radiolytic energy deposition with metabolic reprogramming and immune activation, this strategy establishes boron neutron capture immunotherapy (BNCI) as a multimodal therapeutic paradigm that bridges targeted radiolysis with systemic antitumor immunity.

Boron neutron capture therapy (BNCT) is an emerging targeted radiotherapy technology that enables precise eradication of tumor cells. The development of efficient boron carriers is crucial for the advancement of BNCT technology. Notably, biomolecular carriers currently represent the only class of drug carriers that has achieved market approval (e.g., boronophenylalanine [BPA] in Japan), underscoring their pivotal role in clinical applications. Their outstanding biocompatibility, high payload capacity, and tumor‐targeting capabilities align closely with the stringent requirements of BNCT drug delivery. For instance, amino acid‐based carriers (such as BPA) utilize L‐type amino acid transporter 1 (LAT1) for tumor‐specific accumulation; nucleoside prodrugs are activated by thymidine kinase 1 (TK1) and incorporated into tumor DNA; carbohydrate‐based carriers improve solubility and targeting through glucose transporters (GLUTs); peptide carriers facilitate cellular uptake via receptor‐mediated endocytosis or cell‐penetrating peptides; and liposomes leverage the enhanced permeability and retention (EPR) effect together with active‐targeting modifications for enhanced tumor delivery. Nevertheless, delivering ultrahigh doses of boron remains a major challenge. Biomacromolecules, particularly albumin‐based systems, have garnered increasing attention because of their excellent biosafety and high boron‐loading potential, offering promising avenues for overcoming dose delivery barriers in BNCT. This review systematically summarizes the recent advances in biomolecular carriers for BNCT and highlights emerging applications of protein‐based boron carriers, addressing a notable gap in the comprehensive review of biomolecular strategies within the BNCT drug delivery field.