Metal complexation-mediated stable and biocompatible nanoformulation of clinically approved near-infrared absorber for improved tumor targeting and photonic theranostics

Yong-Deok Lee,Jounghyun Yoo,Sehoon Kim,Joona Bang,Hyeon Jeong Shin,Gayoung Kim,Jae Jun Lee,Jin-Kyoung Yang,Min-Kyoung Kang

doi:10.1186/s40580-021-00286-3

Abstract

Indocyanine green (ICG) is a clinically approved dye that has shown great promise as a phototheranostic material with fluorescent, photoacoustic and photothermal responses in the near-infrared region. However, it has certain limitations, such as poor photostability and non-specific binding to serum proteins, subjected to rapid clearance and decreased theranostic efficacy in vivo. This study reports stable and biocompatible nanoparticles of ICG (ICG-Fe NPs) where ICG is electrostatically complexed with an endogenously abundant metal ion (Fe3+) and subsequently nanoformulated with a clinically approved polymer surfactant, Pluronic F127. Under near-infrared laser irradiation, ICG-Fe NPs were found to be more effective for photothermal temperature elevation than free ICG molecules owing to the improved photostability. In addition, ICG-Fe NPs showed the markedly enhanced tumor targeting and visualization with photoacoustic/fluorescent signaling upon intravenous injection, attributed to the stable metal complexation that prevents ICG-Fe NPs from releasing free ICG before tumor targeting. Under dual-modal imaging guidance, ICG-Fe NPs could successfully potentiate photothermal therapy of cancer by applying near-infrared laser irradiation, holding potential as a promising nanomedicine composed of all biocompatible ingredients for clinically relevant phototheranostics.

Highlights

Photothermal therapy (PTT), a noninvasive light-triggered approach for cancer treatment, has attracted much attention owing to its effective therapeutic outcome withLee et al Nano Convergence (2021) 8:36 nanotubes, graphene, and transition metal sulfide nanoparticles, have been widely explored for PTT ablation [2,3,4,5]
Indocyanine green (ICG) shows excellent light-toheat conversion efficiency as well as a strong PA response [9,10,11]. These outstanding properties make ICG attractive as a photothermal agents (PTAs) for biocompatible theranostic applications wherein NIR fluorescence and/or PA imaging have been combined with phototherapy by PTT
We developed an approach based on the metal complexation of ICG that allows for stable and biocompatible nanoformulation with enhanced disease targetability and theranostic performances

Summary

Introduction

Photothermal therapy (PTT), a noninvasive light-triggered approach for cancer treatment, has attracted much attention owing to its effective therapeutic outcome with. ICG shows excellent light-toheat conversion efficiency as well as a strong PA response [9,10,11] These outstanding properties make ICG attractive as a PTA for biocompatible theranostic applications wherein NIR fluorescence and/or PA imaging have been combined with phototherapy by PTT. The theranostic use of ICG has been limited due to its poor chemical stability in biological environments, nonspecific tissue distribution, propensity to aggregate, poor photostability, and adsorption to serum proteins, resulting in rapid elimination from the body [12] To overcome these limitations, various types of nanoparticles have recently been explored for encapsulating ICG, which can lead to enhanced stability and therapeutic efficacy [13,14,15,16,17]. We successfully applied ICG-Fe NPs for NIR laser-activated PTT of cancer, where only a single operation of PTT caused significance tumor volume suppression that was monitored by MRI imaging

Experimental

Synthesis and characterization of ICG‐Fe NPs

Conclusions