Fluorescence-guided magnetic nanocarriers for enhanced tumor targeting photodynamic therapy.

Abstract

This paper describes a simple approach to develop a multifunctional chlorin e6-hyaluronic-Fe3O4 (Ce6-HA-Fe3O4) theranostic agent. Oleylamine-coated Fe3O4 nanoparticles were prepared through a thermal decomposition route and subsequently transformed into an aqueous phase using hyaluronic acid (HA) via an ultrasonic-assisted emulsion approach. The functional terminal carboxyl groups of the HA outer layer not only promoted the water solubility of Fe3O4 NPs and their targeting ability towards the CD44 overexpressing cancer cells but also allowed straightforward coupling with Ce6. The tumor targeting ability and cellular uptake of the theranostic agent have been demonstrated by magnetic resonance imaging (MRI), confocal microscopy, and flow cytometry (FCM) studies. FCM analysis allowed us to quantify the cellular uptake behavior in response to increased Ce6-HA-Fe3O4 concentration. While no significant toxicity was observed, cell fluorescence signals increased strongly in correlation with the concentration. Analysis on the photodynamic therapeutic (PDT) efficiency tested on B16F1 cells revealed 76.7% cell death under laser irradiation for 10 min (671 nm, 1 W), which is attributed to the successful co-delivery of active Ce6 using HA-Fe3O4 nanocarriers. Taken together, these results indicate that the multifunctional platform retained and combined the original magnetic, fluorescence, and PDT performance of the components in a single remotely triggered nanotheranostic agent. We anticipate that the theranostic agent Ce6-HA-Fe3O4 can act as a promising targeted dual modal probe and a PDT agent to enhance diagnosis and treatment of cancer.