An aptamer-conjugated mesoporous polydopamine formulation for synergistic targeted and photothermal therapy of hepatocellular carcinoma.

This study aimed to create multifunctional nanoparticles (NPs), specifically AS1411@MPDA-Len-Cy5.5 (AMLC), for the purpose of developing effective strategies for treating hepatocellular carcinoma (HCC) through targeted therapy and photothermal therapy (PTT). The study involved synthesizing mesoporous polydopamine (MPDA)-NPs, loading lenvatinib (Len) and Cy5.5 via incubation, and modifying AS1411 aptamer onto MPDA via a covalent chemical reaction. The NPs were characterized using techniques such as ultra-micro spectrophotometry, Fourier transform infrared spectroscopy, and transmission electron microscopy. Target-specific uptake and cell-killing assays were utilized to evaluate AMLC-mediated synergistic therapy while using Western blotting and immunofluorescence to confirm the underlying mechanism. Consequently, the nanoparticles (NPs) were successfully synthesized, demonstrating excellent solvent solubility and stability, with controlled drug release achieved in acidic environments (maximum release efficiency≈80 %). In vitro and in vivo studies revealed that these NPs could more effectively target hepatocellular carcinoma (HCC) cells, enhancing the targeting capability of lenvatinib. Under near-infrared (NIR) laser irradiation, the targeted photothermal therapy (PTT) exhibited significantly improved anticancer efficacy, with AMCL+PTT treatment resulting in up to 76 % tumor volume reduction‌ ( < 0.01). The study demonstrates that AMLC, a multifunctional nano-delivery system, significantly enhances Lenvatinib's tumor-targeting capacity while exhibiting excellent biocompatibility. Combined with photothermal therapy (PTT), it demonstrates potent antitumor efficacy, showing promising clinical translation potential for hepatocellular carcinoma (HCC) therapy.