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

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.

Molecular Tuning of IR-786 for Improved Tumor Imaging and Photothermal Therapy

“…The temperature of the CA800Cl solution rapidly reached approximately 70 °C within the first 30 s of laser irradiation and was maintained up to 80 °C for the next 30 s of irradiation ( Figure 5 b). Based on the equation described in the Materials and Methods section, the photothermal conversion efficiency ( η ) of CA800Cl was calculated to be 30.2%, which is comparable to that of the heptamethine cyanine dyes that were reported previously [ 21 , 22 ]. This suggests that CA800Cl can be used as an effective PTT agent for in vivo photothermal tumor ablation.…”

“…Based on the equation reported previously [ 21 , 22 ], the photothermal conversion efficiency ( η ) of the CA800Cl NIR fluorophore was calculated as follows:…”

Renal clearable bone-targeted contrast agents for theranostic imaging

“…S3b). This result is consistent with the known photothermal effect of ZW800-PEG, where the incident photons are absorbed and converted into heat energy [38][39][40]. Among them.…”

Enhanced Tumor Accumulation of Low-Molecular-Weight Hyaluronic Acid/Chitosan Nanocomplexes for Photothermal Therapy

“…LMW-HA (average MW ≈ 8000–15,000 Da) and COL (average MW ≈ 5000 Da, >90% deacetylated form) were purchased from Sigma-Aldrich (St. Louis, MO, USA) and used without further purification. The amine-functionalized zwitterionic NIR dye (ZW800-AM) and carboxyl-functionalized zwitterionic NIR dye (ZW800-1) were prepared as described previously [ 26 , 27 , 28 , 29 ]. For HA-ZW, ZW800-AM (0.8 mg, 0.87 μmol) was conjugated to LMW-HA (10 mg, 0.87 μmol) in the presence of 4-(4,6-dimethoxy-1,3,5-triazin-2-yl)-4-methylmorpholinium chloride (DMT-MM; 0.5 mg, 1.8 μmol) in distilled water (DW, 1 mL) at ambient temperature for 12 h. For COL-ZW, ZW800-1 (1.9 mg, 2 μmol) was used to conjugate with COL (10 mg, 2 μmol) in the presence of DMT-MM (0.8 mg, 3 μmol) in DW (1 mL) at ambient temperature for 12 h. The crude mixtures of HA-ZW and COL-ZW were dialyzed against DW using a dialysis membrane tube (MWCO 3.5 kDa) to eliminate free dyes and coupling agents, respectively.…”