pH-Responsive Near Infrared Light Triggered Hydroxyapatite Nanoparticles for Targeted Photothermal Cancer Therapy

Photothermal therapy (PTT), which utilizes photothermal agents (PTAs) to induce localized hyperthermia within tumors upon light irradiation, has emerged as a promising cancer treatment strategy. However, low water solubility, poor in vivo circulation stability and a lack of tumor specificity of many common PTAs limit their applicability. To address these issues, we have developed a simple, yet highly potent, tumor-targeted nanotheranostic system that consists of lipid/PEG-coated hydroxyapatite nanoparticles (LHAPNs) encapsulating the near-infrared (NIR) photothermal dye IR106 (LHAPNIRs). The lipid coat serves to retain the encapsulated dye and prevent serum protein adsorption and macrophage recognition, which would otherwise destabilize the nanoparticles and hinder their tumor targeting efficiency. Additionally, the coat is functionalized with the tumor-acidity-triggered rational membrane (ATRAM) peptide for efficient and specific internalization into tumor cells in the mildly acidic microenvironment of tumors. The nanoparticles facilitated real-time fluorescence and thermal imaging of tumors and demonstrated potent NIR-light triggered anticancer activity in vitro and in vivo, without adversely affecting healthy tissue, leading to markedly prolonged survival. Our results demonstrate that the biocompatible and biodegradable ATRAM-functionalized LHAPNIRs (ALHAPNIRs) effectively combine dual-mode diagnostic imaging with targeted cancer PTT.