A pH-responsive nanoplatform with dual-modality imaging for enhanced cancer phototherapy and diagnosis of lung metastasis

J Nanobiotechnology. 2024 Apr 15;22(1):180. doi: 10.1186/s12951-024-02431-6.

Abstract

To address the limitations of traditional photothermal therapy (PTT)/ photodynamic therapy (PDT) and real-time cancer metastasis detection, a pH-responsive nanoplatform (NP) with dual-modality imaging capability was rationally designed. Herein, 1 H,1 H-undecafluorohexylamine (PFC), served as both an oxygen carrier and a 19F magnetic resonance imaging (MRI) probe, and photosensitizer indocyanine green (ICG) were grafted onto the pH-responsive peptide hexahistidine (H6) to form H6-PFC-ICG (HPI). Subsequently, the heat shock protein 90 inhibitor, gambogic acid (GA), was incorporated into hyaluronic acid (HA) modified HPI (HHPI), yielding the ultimate HHPI@GA NPs. Upon self-assembly, HHPI@GA NPs passively accumulated in tumor tissues, facilitating oxygen release and HA-mediated cell uptake. Once phagocytosed by lysosomes, protonation of H6 was triggered due to the low pH, resulting in the release of GA. With near-infrared laser irradiation, GA-mediated decreased HSP90 expression and PFC-mediated increased ROS generation amplified the PTT/PDT effect of HHPI@GA, leading to excellent in vitro and in vivo anticancer efficacies. Additionally, the fluorescence and 19F MRI dual-imaging capabilities of HHPI@GA NPs enabled effective real-time primary cancer and lung metastasis monitoring. This work offers a novel approach for enhanced cancer phototherapy, as well as precise cancer diagnosis.

Keywords: Dual-modality fluorescence/19F MRI; Enhanced phototherapy; Lung metastasis; pH-responsive.

MeSH terms

  • Cell Line, Tumor
  • Humans
  • Hydrogen-Ion Concentration
  • Indocyanine Green
  • Lung Neoplasms* / diagnostic imaging
  • Lung Neoplasms* / therapy
  • Nanoparticles*
  • Oxygen
  • Photochemotherapy*
  • Phototherapy / methods

Substances

  • Indocyanine Green
  • Oxygen