Targeted dual-mode imaging and phototherapy of tumors using ICG-loaded multifunctional MWCNTs as a versatile platform

Abstract

We present the development of indocyanine green (ICG)-loaded and folic acid (FA)-modified multiwalled carbon nanotubes (MWCNTs) as a versatile nanoplatform for targeted dual-mode fluorescence (FL)/photoacoustic (PA) imaging, and photothermal therapy (PTT)/photodynamic therapy (PDT) of tumors in vivo. In this study, acid-treated MWCNTs with carboxyl residues were first covalently conjugated with polyethyleneimine (PEI). This was followed by sequential modification of FA via a polyethylene glycol (PEG) segment, fluorescein isothiocyanate (FITC), and succinic anhydride (SAH), multifunctional FA-modified MWCNTs (MWCNT–PEI·SAH–FITC–PEG–FA) were formed. The functional MWCNTs possess exceptional colloidal stability, good hemocompatibility/cytocompatibility in a studied concentration range, and targeting specificity to FA receptor-overexpressing cancerous cells. Via π–π stacking interactions, the MWCNTs enable highly efficient loading of ICG and the ICG-loaded MWCNTs exhibit excellent photostability and can be used for FL imaging/PDT of tumors due to the singlet oxygen (¹O₂) generation from ICG. In addition, the near-infrared absorption characteristic of ICG also renders the MWCNT nanoplatform with a capacity for simultaneous PA imaging and PTT of tumors. Our study reports a novel theranostic nanosystem that can be used for targeted dual-mode FL/PA imaging and PTT/PDT of tumors in vivo, which may show profound promise for translation into clinical uses.