ArticleInternational journal of nanomedicine2025
Multi-Focused Acoustic Radiation Force Impulse Modulation of Murine Hepatic Xenografts Enhances Nanoscale DOX@Lip Delivery and Therapeutic Effect.
Article in International journal of nanomedicine, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.
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2 authors.
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Abstract
Purpose: To investigate whether multi-focused acoustic radiation force impulse (MF-ARFI) applied to murine xenograft liver tumors prior to intravenous administration of doxorubicin-loaded PEGylated liposomes (DOX@Lip) can enhance drug delivery efficiency through modulating the enhanced permeation and retention effect of the tumor, reduce side effects, and improve antitumor effect. Materials and Methods: DOX@Lip and tumor-mimetic matrices were synthesized and characterized. Huh-7 cells and DOX@Lip were exposed to MF-ARFI and observed. MF-ARFI was applied to both tumor-mimetic matrices and saline with DOX@Lip to assess displacement effects. Subsequently, murine xenograft models were established and underwent MF-ARFI preconditioning before DOX@Lip injection. Tumor volume dynamics and body weight changes were longitudinally monitored. Terminal assessments included histopathology (H&E), apoptosis (TUNEL), and molecular profiling (BCL-2 and BAX by Western blot) of tumors and major organs. Results: There was no significant difference in the live/dead cell staining results between the Huh7 cells with and without MF-ARFI. There was no significant difference in cell apoptosis rates of Huh7 cells between DOX@Lip and DOX@Lip+MF-ARFI. MF-ARFI exposure induced measurable displacement of DOX@Lip in both tumor-mimetic matrices and saline. Mice receiving combined DOX@Lip and MF-ARFI treatment exhibited significantly attenuated tumor growth (p<0.05) and slight weight loss, which were significantly different from DOX and DOX+MF-ARFI treatments. Cardiac histopathology revealed no significant differences in myocardial toxicity between DOX@Lip and DOX@Lip+MF-ARFI groups relative to PBS controls. Conversely, tumors from the DOX@Lip+MF-ARFI group demonstrated distinct histopathological alterations compared to other groups. TUNEL staining results indicated a relatively higher level of cell apoptosis in mice treated with DOX@Lip+MF-ARFI. Molecular analyses showed MF-ARFI pretreatment significantly reduced BCL-2 expression (p<0.05) while elevating the BAX/BCL-2 ratio versus DOX@Lip monotherapy. Conclusion: Preconditioning xenograft tumors with MF-ARFI prior to DOX@Lip administration faciliates DOX@Lip delivery and significantly enhances antitumor effect while reducing cardiotoxicity. This combinatorial strategy demonstrates translational potential for optimizing liposomal chemotherapeutic delivery and effect.
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