NIR-II Photoacoustic Imaging-Guided Oxygen Delivery and Controlled Release Improves Photodynamic Therapy for Hepatocellular Carcinoma.

Hypoxia, a prominent hallmark of hepatocellular carcinoma (HCC), undermines curative outcomes, elevates recurrence rates, and fosters metastasis, particularly during photodynamic therapy (PDT) in clinical settings. Studies indicate that alleviating tumor hypoxia enhances PDT efficacy. However, persistent challenges, including suboptimal oxygen delivery efficiency and absence of real-time feedback on blood oxygen fluctuations during PDT, considerably impede therapeutic efficacy in tumor treatment. This study addresses these issues using near-infrared-II (NIR-II) photoacoustic (PA) imaging for tumor-targeted oxygen delivery and controlled release. For this purpose, a biomimetic oxygen delivery system designated BLICP@O2 is developed, which utilizes hybrid tumor cell membranes and thermosensitive liposomes as oxygen carriers, incorporating the NIR-II dye IR1048, photosensitizer chlorin e6 (Ce6), and perfluorohexane. Upon sequential irradiation at 1064 and 690 nm, BLICP@O2 exhibits significant photothermal and photodynamic effects. Photothermal heating triggers oxygen release, enhancing the photodynamic effect of Ce6. Blood oxygen changes during PDT are tracked by multispectral PA imaging. Enhanced PDT efficacy, mediated by hypoxia relief, is convincingly demonstrated both in vitro and in vivo. This work presents an imaging-guided, dual-wavelength programmed cascaded treatment strategy for tumor-targeted oxygen delivery and controlled release, with real-time efficacy monitoring using PA imaging, offering valuable insights for overcoming challenges in PDT-based cancer therapy.

Identification of chromosomal instability-associated genes as hepatocellular carcinoma progression-related biomarkers to guide clinical diagnosis, prognosis and therapy.

Hepatocellular carcinoma (HCC) is a type of cancer characterized by high heterogeneity and a complex multistep progression process. Significantly-altered biomarkers for HCC need to be identified. Differentially expressed genes and weighted gene co-expression network analyses were used to identify progression-related biomarkers. LASSO-Cox regression and random forest algorithms were used to construct the progression-related prognosis (PRP) score. Three chromosomal instability-associated genes (KIF20A, TOP2A, and TTK) have been identified as progression-related biomarkers. The robustness of the PRP scores were validated using four independent cohorts. Immune status was observed using the single-sample gene set enrichment analysis (ssGSEA). Comprehensive analysis showed that the patients with high PRP score had wider genomic alterations, more malignant phenotypes, and were in a state of immunosuppression. The diagnostic models constructed via logistic regression based on the three genes showed satisfactory performances in distinguishing HCC from cirrhotic tissues or dysplastic nodules. The nomogram combining PRP scores with clinical factors had a better performance in predicting prognosis than the tumor node metastasis classification (TNM) system. We further confirmed that KIF20A, TOP2A, and TTK were highly expressed in HCC tissues than in cirrhotic tissues. Downregulation of all three genes aggravated chromosomal instabilities in HCC and suppressed HCC cells viability both in vitro and in vivo. Overall, our study highlights the important roles of chromosomal instability-associated genes during the progression of HCC and their potential clinical diagnosis and prognostic value and provides promising new ideas for developing therapeutic strategies to improve the outcomes of HCC patients.