Tumor-targeted hydroxyapatite nanoparticles for near-infrared II light-mediated dual-mode diagnostic imaging and photothermal cancer therapy

Photothermal therapy (PTT) utilizes photothermal agents (PTAs) to induce localized hyperthermia within tumors upon light irradiation. However, low solubility, poor circulation stability, and lack of tumor specificity of common PTAs limit their applicability. To address these issues, we have developed a simple tumor-targeted nanotheranostic system consisting of lipid/PEG-coated hydroxyapatite nanoparticles (LHAPNs) encapsulating the near-infrared II (NIR-II) photothermal dye IR1061 (LHAPNIRs). The lipid coat retains encapsulated dye and prevents serum protein adsorption, which would otherwise destabilize the nanoparticles (NPs) and impede tumor targeting. Additionally, the coat is functionalized with the acidity-triggered rational membrane (ATRAM) peptide for efficient and specific internalization into cancer cells in the mildly acidic microenvironment of tumors. The NIR-II activated NPs facilitate real-time fluorescence and thermal imaging of tumors and exhibit potent anticancer activity without adversely affecting healthy tissue. Our results demonstrate that the biocompatible and biodegradable ATRAM-functionalized LHAPNIRs effectively combine dual-mode diagnostic imaging with targeted cancer PTT.