Tumor-Targeted ZW800-1 Analog for Enhanced Tumor Imaging and Photothermal Therapy.

Min-Ho Park,Eun-Jeong Kim,Hoon Hyun,Gayoung Jo

doi:10.3390/pharmaceutics13101648

Min-Ho Park, Eun-Jeong Kim + Show 2 more

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https://doi.org/10.3390/pharmaceutics13101648

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Abstract

ZW800-1, a representative zwitterionic near-infrared (NIR) fluorophore, can minimize background tissue uptake owing to its balanced surface charges, and therefore, is widely used for improved NIR fluorescence imaging. As ZW800-1 has no tumor targetability, tumor imaging is highly dependent on the ability of the molecules conjugated to the ZW800-1. To enable tumor targeting using ZW800-1 without additional conjugation, we developed a tumor-targetable and renal-clearable ZW800-1 analog (ZW800-AM) based on the structural modification of ZW800-1. Specifically, an amine group on the center linker of the ZW800-1 indocyanine backbone was modified by replacing phenoxypropionic acid with tyramine linkage on the meso-chlorine atom. This modification improved the tumor targeting ability, which is known as the structure-inherent targeting strategy. More importantly, ZW800-AM not only showed sufficient tumor accumulation without nonspecific uptake but also produced a photothermal effect, killing tumor cells under 808 nm NIR laser irradiation. In addition, ZW800-AM exhibited rapid renal elimination from the body within 4 h of injection, similar to ZW800-1. Overall, the discovery of ZW800-AM as a bifunctional phototherapeutic agent may provide an ideal alternative for tumor-targeted imaging and phototherapy.

Highlights

We report for the first time the tumor-targeting ability of ZW800-AM, which is an aminated form of ZW800-1, without additional conjugation with tumor-targeting ligands
We identified a zwitterionic NIR fluorophore, ZW800-AM as a ZW8001 analog, which could be used for tumor-targeted imaging and Photothermal therapy (PTT) simultaneously without further conjugation with tumor-specific ligands and photosensitizers
We identified a zwitterionic NIR fluorophore, ZW800-AM as a ZW800-1 analog, which could be used for tumor-targeted imaging and PTT simultaneously without further conjugation with tumor-specific ligands and photosensitizers

Summary

Introduction

The development of functional near-infrared (NIR) fluorophores with both targetspecific imaging and cancer therapy capabilities has become of paramount importance for practical applications in NIR light-mediated photothermal cancer treatment [1,2,3]. Photothermal therapy (PTT), which is based on the principle of light-to-heat conversion, is a local and noninvasive cancer treatment approach by hyperthermia after administration of photosensitizers, leading to cancer cell death [4]. Among cyanine-based photosensitizers, the most well-known and the only clinically approved NIR fluorophore is indocyanine green (ICG) [5,6]. ICG has limitations in target-specific in vivo imaging owing to its poor bioavailability (e.g., solubility and stability), high liver uptake, and lack of functional groups for chemical conjugation with targeting molecules [7,8,9]. Despite the significant improvements in ZW800-1 properties compared to those of other conjugatable NIR fluorophores (e.g., IRDye800CW and Cy5.5), the fundamental problem of low targeting efficiency is still unsolved because the targetability of ligands could be altered after conjugation [19]

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