Multi-responsive albumin-lonidamine conjugated hybridized gold nanoparticle as a combined photothermal-chemotherapy for synergistic tumor ablation

摘要

Herein, we developed a multifunctional nanoplatform based on the nanoassembly of gold nanoparticles (GNP) conjugated with lonidamine (LND) and aptamer AS1411 (AS-LAGN) as an effective cancer treatment. Conjugating AS1411 aptamer on the surface of the nanoparticle significantly improved particle accumulation in cancer cells via specific affinity toward the nucleolin receptors. In vitro study clearly revealed that laser irradiation-based hyperthermia effect enhanced the chemotherapeutic effects of LND. Combinational treatment modalities revealed significant apoptosis with higher cell killing effect due to increased ROS production and inhibition of cell migration. GNP's ability to convert the excited state photon energy into thermal heat enabled synergistic photothermal/chemotherapy with improved therapeutic efficacy in animal models. Moreover, immunohistochemistry staining assays confirmed the ability of ASLAGN to induce cellular apoptosis/necrosis and ablation in tumor tissues, without causing evident damages to the surrounding healthy tissues. Altogether, this AS-LAGN nanoplatform could be a promising strategy for mitochondria-based cancer treatment.