Relative to traditional photosensitizer (PS) agents, those that exhibit aggregation-induced emission (AIE) properties offer key advantages in the context of photodynamic therapy (PDT). At present, PDT efficacy is markedly constrained by the hypoxic microenvironment within tumors and the limited depth to which lasers can penetrate in a therapeutic context. Herein, we developed platelet-mimicking MnO₂ nanozyme/AIEgen composites (PMD) for use in the interventional PDT treatment of hypoxic tumors. The resultant biomimetic nanoparticles (NPs) exhibited excellent stability and were able to efficiently target tumors. Moreover, they were able to generate O₂ within the tumor microenvironment owing to their catalase-like activity. Notably, through an interventional approach in which an optical fiber was introduced into the abdominal cavity of mice harboring orthotopic colon tumors, good PDT efficacy was achieved. We thus propose that a novel strategy consisting of a combination of an AIEgen-based bionic nanozyme and a biomimetic cell membrane coating represents an ideal therapeutic platform for targeted antitumor PDT. This study is the first to have combined interventional therapy and AIEgen-based PDT, thereby overcoming the limited light penetration that typically constrains the therapeutic efficacy of this technique, highlighting a promising new AIEgen-based PDT treatment strategy.

Purpose: In spite of its enhanced efficacy and reduced side effects in clinical hepatocellular carcinoma (HCC) therapy, the therapeutic efficacy of antitumor angiogenesis inhibitor sorafenib (SFB) is still restricted due to short in vivo half-life and drug resistance. Here, a novel SFB-loaded dendritic polymeric nanoparticle (NP-TPGS-SFB) was developed for enhanced therapy of HCC. Methods: NP-TPGS-SFB was fabricated by encapsulating SFB with biodegradable dendritic polymers poly(amidoamine)-poly(γ-benzyl-L-Glutamate)-b-D-α-tocopheryl polyethylene glycol 1000 succinate (PAM-PBLG-b-TPGS). Results: NP-TPGS-SFB exhibited excellent stability and achieved acid-responsive release of SFB. It also exhibited much higher cellular uptake efficiency in HepG2 human liver cells than PEG-conjugated NP (NP-PEG-SFB). Furthermore, MTT assay confirmed that NP-TPGS-SFB induced higher cytotoxicity than NP-PEG-SFB and free SFB, respectively. Lastly, NP-TPGS-SFB significantly inhibited tumor growth in mice bearing HepG2 xenografts, with negligible side effects. Conclusion: Our result suggests that NP-TPGS-SFB may be a novel approach for enhanced therapy of HCC with promising potential.

This analysis aimed to investigate whether the long-term administration of temozolomide (TMZ) claimed a survival advantage for patients with glioblastoma in China. A total of 75 patients with newly diagnosed glioblastoma at the Department of Radiation Oncology, Shenzhen People's Hospital between August 2008 and August 2016 were retrospectively evaluated during analysis. A propensity-matched analysis was performed to balance the basic characteristics of patients between compared groups. Kaplan–Meier method and Cox proportional hazards model were used to assess progression-free survival (PFS) and overall survival (OS) of patients receiving 6 adjuvant TMZ cycles compared with patients treated with more than 6 cycles. Twenty of 75 patients received more than 6 cycles of TMZ, and the other 55 patients were treated with a median of 6 cycles ranging from 1 to 6. The patients with long-term administration of TMZ had better OS (47.0 months, 95% CI 20.0–73.9 vs 20.6 months, 95% CI 17.9–23.2, P = .014) but not PFS (17.0 months, 95% CI 10.1–24.5 vs 14.2 months, 95% CI 11.8–16.6, P = .133). Balancing the clinical factors with a propensity-matched analysis also showed the significant advantage of prolonged TMZ application in terms of OS but not PFS. Prolonged administration of TMZ beyond 6 cycles did demonstrate survival benefits for patients with initially diagnosed glioblastoma.

In oncogenesis and development of malignant tumor, microRNAs (miRNAs) regulate the complex gene expression associated with the tumor pathogenesis. Currently, only few studies have been conducted to identify miRNAs and the potential pathways involved in the pathogenesis of brain metastasis in patients who underwent radiotherapy, especially miRNAs in the plasma exosomes. Therefore, this study is aimed to use small RNA analysis to identify miRNAs and their potential target genes in plasma exosomes during the initiation and development of brain metastasis in patients who underwent radiotherapy. Using high-throughput sequencing technologies, we identified 35 differentially expressed miRNAs in patients with brain metastasis who had undergone radiotherapy. In annotation of miRNA targets, gene ontology enrichment analysis revealed that the targets of the differentially expressed miRNAs were significantly enriched in the regulation of cellular processes. Kyoto Encyclopedia of Genes and Genomes revealed that most of the miRNA targets were cancer-related, including genes involved in the mitogen-activated protein kinase signaling pathway, cancer-related pathways, phosphatidylinositol 3-kinase-protein kinase B signaling pathway, microtubule-associated protein kinase signaling pathway, Ras signaling pathway, regulation of the actin cytoskeleton, and axon guidance. In conclusion, this study provides a new perspective to understand the possible function of these miRNAs in the pathogenesis of brain metastasis. This was the first time that a pilot study identified plasma exosomal miRNAs in five patients with brain metastasis before and after radiotherapy. This study is the beginning; more specimen and further research are needed to explore the functional role of specific miRNAs and their potential as therapeutic targets for brain metastasis.

Objectives: Glioblastoma (GBM) is the most common malignant primary brain tumor with local recurrence after radiotherapy (RT), the most common mode of failure. Standard RT practice applies the prescription dose uniformly across tumor volume disregarding radiological tumor heterogeneity. We present a novel strategy using diffusion-weighted (DW-) MRI to calculate the cellular density within the gross tumor volume (GTV) in order to facilitate dose escalation to a biological target volume (BTV) to improve tumor control probability (TCP). Methods: The pre-treatment apparent diffusion coefficient (ADC) maps derived from DW-MRI of ten GBM patients treated with radical chemoradiotherapy were used to calculate the local cellular density based on published data. Then, a TCP model was used to calculate TCP maps from the derived cell density values. The dose was escalated using a simultaneous integrated boost (SIB) to the BTV, defined as the voxels for which the expected pre-boost TCP was in the lowest quartile of the TCP range for each patient. The SIB dose was chosen so that the TCP in the BTV increased to match the average TCP of the whole tumor. Results: By applying a SIB of between 3.60 Gy and 16.80 Gy isotoxically to the BTV, the cohort’s calculated TCP increased by a mean of 8.44% (ranging from 7.19 to 16.84%). The radiation dose to organ at risk is still under their tolerance. Conclusions: Our findings indicate that TCPs of GBM patients could be increased by escalating radiation doses to intratumoral locations guided by the patient’s biology (i.e., cellularity), moreover offering the possibility for personalized RT GBM treatments. Advances in knowledge: A personalized and voxel level SIB radiotherapy method for GBM is proposed using DW-MRI, which can increase the tumor control probability and maintain organ at risk dose constraints.

Triple-negative breast cancer (TNBC) is associated with a high risk of brain metastases (BMs). Although systemic therapies have improved extracranial disease control, the central nervous system (CNS) remains less accessible to numerous agents. As a result, this limited drug penetration makes brain metastases (BMs) remain common in TNBC, which are a leading cause of serious symptoms. This review summarizes recent key advances in triple-negative breast cancer brain metastases (TNBC-BMs), including epidemiology, prognostic stratification, biological mechanisms of CNS tropism and treatment resistance, and evolving management strategies. We discuss potential mechanisms of brain colonization, including the FOXC1-CXCR4 axis, ST6GALNAC5-related interactions with the blood–brain barrier (BBB), and the bidirectional crosstalk between metastatic cells and the brain microenvironment, particularly astrocytes and microglia. Furthermore, we evaluate the evolving clinical management, emphasizing the transition from whole-brain radiotherapy (WBRT) toward more selective local approaches such as stereotactic radiotherapy (SRS) and hippocampal sparing techniques. Concurrently, we examine the integration of CNS active systemic therapy across specific molecular subsets. This review systematically distinguishes standard-of-care interventions from investigational strategies, ultimately underscoring critical evidence gaps within the TNBC-BM landscape.