Controlled Synthesis and Surface Engineering of Janus Chitosan‐Gold Nanoparticles for Photoacoustic Imaging‐Guided Synergistic Gene/Photothermal Therapy

Abstract The unsymmetrical morphology and unique properties of Janus nanoparticles (JNPs) provide superior performances for biomedical applications. In this work, a general and facile strategy is developed to construct a series of symmetrical and unsymmetrical chitosan/gold nanoparticles. Taking advantage of the active motion derived from Janus structure, selective surface functionalization of polysaccharide domain, and photothermal effect of gold nanorods, Janus chitosan/gold nanoparticles (J‐Au‐CS) are selected as a model system to construct Janus‐structured chitosan/gold nanohybrids (J‐ACP). Near‐infrared (NIR)‐responsive J‐ACP composed of polycationic chitosan nanospheres and PEGylated gold nanorods hold great potential to realize photoacoustic (PA) imaging‐guided complementary photothermal therapy (PTT)/gene therapy for breast cancer. The morphology effect of chitosan/gold nanostructures on enhanced PTT, cellular uptake, and gene transfection is investigated. The feasibility of PA imaging to track the accumulation of J‐ACP and guide PTT is also explored. Notably, synergistic therapy is achieved based on PTT‐enhanced gene therapy. In addition, the loading function of chitosan/gold nanoparticles for fluorescence imaging is demonstrated. The current work extends the application of JNPs for imaging‐guided synergistic cancer therapy and provides flexible candidates with distinct structures for diverse biomedical applications.