Acid-triggered in vivo aggregation of Janus nanoparticles for enhanced imaging-guided photothermal therapy

Poor tumor delivery efficiency remains a significant challenge for the integrated nanoplatform for diagnosis and treatment. Nanotherapeutics capable of aggregation in response to the tumor microenvironment has received considerable attention because of its ability to enhance tumor delivery efficiency and accumulation. We prepared smart Au-Fe₃O₄ Janus nanoparticles (GIJ NPs) modified with mixed-charged ligands (3,4-dihydroxyhydrocinnamic acid [DHCA] and trimethylammonium dopamine [TMAD]). The obtained GIJ@DHCA-TMAD could be stable at the pH of the blood and normal tissues, but aggregated into larger particles in response to the tumor acidic microenvironment, leading to greatly enhanced accumulation in cancer cells. The hydrodynamic diameters of GIJ@DHCA-TMAD increased from 28.2 to 105.7 nm when the pH decreased from 7.4 to 5.5. Meanwhile, the T ₂ magnetic resonance imaging (MRI) contrast capability, photoacoustic imaging (PAI) performance, and photothermal conversion efficiency of GIJ@DHCA-TMAD were also enhanced with increasing diameter. Tumor-specific enhanced MRI and PAI can precisely locate tumor boundaries and can be used to perform preliminary photothermal tumor ablation therapy: the pH-sensitive GIJ@DHCA-TMAD can be used in dual-mode, tumor-specific imaging-guided photothermal therapy to better meet the multiple requirements for in vivo applications.