Abstract

One of the bottlenecks for hepatocellular carcinoma (HCC) treatment is that most patients are diagnosed at an advanced stage, making the tumor unresectable. Meanwhile, the efficiency of conversion therapy and surgical resection for HCC treatment is still unsatisfactory. Here, an ultra-stable homogeneous lipiodol compound formulation was generated to achieve efficient HCC downstaging and precise surgical navigation simultaneously. The chemotherapeutic drug doxorubicin hydrochloride (DOX) and the surgical navigation contrast agent indocyanine green (ICG) were prepared into carrier-free nanoparticles (DOX&ICG NPs), and then dispersed in lipiodol to prepare superstable homogeneous DOX&ICG@lipiodol formulation (SHIFT DIL). Subsequently, models of transparent liver, rabbit ear tumor, and rabbit VX2 orthotopic liver cancer were constructed to verify that SHIFT DIL has the characteristics of excellent stability, tumor-specific deposition, and slow drug release. The chemotherapy effect is remarkable and tumor downstaging was successfully achieved. In particular, ICG exhibits particularly good specificity in cancer focus concurrently, and accurately displaying the tumor area with a strong fluorescence signal, which higher 1.5 times than that of free ICG intravenous injection, thus enabling accurate and efficient surgical resection guided by fluorescence navigation. We elucidate that when SHIFT DIL was embolized into the tumor focus, DOX can continuously induce tumor cell death, and then ICG can be better deposited into the damaged cells and display a brighter fluorescence signal. We also demonstrate that the ICG deposition process is not limited by the degree of HCC differentiation. Therefore, SHIFT DIL has the function of universal precise surgical navigation after HCC conversion therapy, and along with great clinical transformation prospects.

文章链接：https://doi.org/10.1016/j.cclet.2026.113031