Thermosensitive RGD-modified liposomes co-loading Fe₃O₄ and sorafenib for synergistic photothermal-chemotherapy of hepatocellular carcinoma.

Authors

Sizhan Peng, Lifeng Hang, Xiaofeng Li, Haoran Zhang, Jinlin Nie, Kaiqiang He, Wei Huang, Xiaoyan Shi, Yang Liu, Hailiang Li

Published in

Dalton transactions (Cambridge, England : 2003). Oct 16, 2026. Epub Oct 16, 2026.

Abstract

Sorafenib (SRF) therapy for hepatocellular carcinoma (HCC) is limited by dose-limiting toxicities, inadequate tumor exposure, and the inability to confine drug action spatiotemporally, leading to suboptimal efficacy and a narrow therapeutic window. Here we report an RGD-functionalized DPPC-based thermosensitive liposomal theranostic system co-encapsulating Fe₃O₄ nanoparticles and SRF (RGD-Fe₃O₄/SRF@TSL) to enable MRI-guided window selection and near-infrared (NIR)-triggered, on-demand chemotherapy potentiation. The nanosystem is colloidally stable (208 nm) and exhibits a phase transition at 41 °C. Accordingly, SRF release is sharply temperature-gated, reaching 88% at 45 °C but only 26% at 37 °C within 18 h (3.4-fold enhancement). Fe₃O₄ confers strong T₂ MRI contrast (r₂ = 136.4 mM^-1 s^-1) and photothermal conversion (η = 24.73%), enabling noninvasive tracking of tumor accumulation and controllable local heating that elevates tumor-surface temperature to 56 °C within 5 min under 808 nm irradiation. Dynamic MRI identifies a pronounced tumor signal drop at ∼12 h post-injection, providing an imaging-defined irradiation window. RGD decoration improves cellular internalization (DiO-positive cells 80.6% vs. 55.8% at 3 h) and, together with NIR activation, increases ROS-associated signals, mitochondrial depolarization, and apoptosis (up to 46.4%) in vitro. In Hepa1-6 tumor-bearing mice, the image-guided combined regimen markedly suppresses tumor growth, reducing endpoint tumor weight from 1.1 g (PBS) to 0.1 g (91% reduction) without obvious acute toxicity under the tested conditions. This work establishes an operational "MRI-defined window → mild hyperthermia → thermosensitive release" paradigm to localize SRF action and improve the efficacy-toxicity balance for HCC therapy.

PMID:
42885555
Bibliographic data and abstract were imported from PubMed on 16 Oct 2026.

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