This study aimed to perform hemodynamic simulations using patient-specific models of abdominal aortic aneurysms (AAA) following endovascular aneurysm repair (EVAR) to investigate the association between energy loss (EL) and Type I endoleak.
Pre- and post-EVAR models were reconstructed from computed tomography angiography (CTA) for four patients with Type I endoleak and four without. Component quantification of EL, along with wall shear stress (WSS)-related hemodynamic parameters, were employed to evaluate the potential of endoleak.
Endoleaks following EVAR tended to occur at the junction of stent grafts, where high time-averaged wall shear stress (TAWSS), high turbulence EL, and high mean flow EL were observed. The turbulence EL values for the main stents, left iliac branch stents, and right iliac branch stents in the endoleak group were 516 ± 183*10
−6
W, 828 ± 195*10
−6
W, and 609 ± 193*10
−6
W, respectively, and the mean flow EL for those regions were 363 ± 125*10
−6
W, 631 ± 138*10
−6
W, and 352 ± 162*10
−6
W, respectively. Compared with the no endoleak group, the endoleak group exhibited significantly higher turbulence EL and mean flow EL at the iliac branch and main stent, whereas no significant difference in TAWSS was found.
Component quantification of EL demonstrated preliminary feasibility for evaluating Type I endoleak in patients with EVAR for AAA, demonstrating greater advantages over WSS-related hemodynamic parameters. This method may provide valuable support for clinicians in assessing surgical prognosis.
Ran Tao, Qiming Liu, Weihao Guo et al.· Frontiers in Cardiovascular...· 0 citations
BACKGROUND
Navitoclax (ABT-263) exhibits strong cytotoxic effects against hepatocellular carcinoma cells in vitro; however, its therapeutic efficacy in vivo is limited by insufficient local drug accumulation and compensatory upregulation of the anti-apoptotic protein myeloid cell leukemia-1 during long-term treatment. In addition, effective immune activation in hepatocellular carcinoma remains challenging due to the immune-privileged hepatic microenvironment. This study aimed to overcome these limitations through a tumor-targeted nanotherapeutic strategy.
RESULTS
Dual pH-responsive copolymeric nanoparticles modified with folic acid and co-loaded with navitoclax and indocyanine green (FPNAI) were developed. FPNAI preferentially accumulated at hepatocellular carcinoma sites through folate receptor-mediated targeting and released navitoclax in response to the acidic tumor microenvironment, thereby inducing mitochondria-mediated apoptosis. Upon near-infrared irradiation, indocyanine green generated excessive reactive oxygen species, leading to downregulation of myeloid cell leukemia-1 and further enhancement of apoptotic signaling. The combined effects of navitoclax and reactive oxygen species synergistically promoted tumor cell apoptosis. Moreover, apoptosis induced by FPNAI triggered immunogenic cell death, characterized by dendritic cell maturation and activation of cytotoxic CD8⁺ T cells. In vivo studies demonstrated that FPNAI with near-infrared irradiation achieved significantly improved antitumor efficacy compared with navitoclax monotherapy, while maintaining favorable tumor-targeting capability and biosafety.
CONCLUSIONS
This study demonstrates that FPNAI enhances the antitumor activity of navitoclax by integrating targeted drug delivery, reactive oxygen species-mediated mitochondrial apoptosis, and immunogenic cell death induction. The proposed nanotherapeutic platform represents a promising approach for improving hepatocellular carcinoma treatment outcomes.
Jiahao Wang, Tianao Xie, Heng Jiang et al.· Journal of Nanobiotechnology· 0 citations
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