ABSTRACT
Poorly identified tumor boundaries and nontargeted therapies lead to the high recurrence rates and poor quality of life of prostate cancer patients. Near-infrared-II (NIR-II) fluorescence imaging provides certain advantages, including high resolution and the sensitive detection of tumor boundaries. Herein, a cyanine agent (CY7-4) with significantly greater tumor affinity and blood circulation time than indocyanine green was screened. By binding albumin, the absorbance of CY7-4 in an aqueous solution showed no effects from aggregation, with a peak absorbance at 830 nm and a strong fluorescence emission tail beyond 1000 nm. Due to its extended circulation time (half-life of 2.5 h) and high affinity for tumor cells, this fluorophore was used for primary and metastatic tumor diagnosis and continuous monitoring. Moreover, a high tumor signal-to-noise ratio (up to ~ 10) and excellent preferential mitochondrial accumulation ensured the efficacy of this molecule for photothermal therapy. Therefore, we integrated NIR-II fluorescence-guided surgery and intraoperative photothermal therapy to overcome the shortcomings of a single treatment modality. A significant reduction in recurrence and an improved survival rate were observed, indicating that the concept of intraoperative combination therapy has potential for the precise clinical treatment of prostate cancer.
Subject(s)
Carbocyanines , Mitochondria , Neoplasm Recurrence, Local , Photothermal Therapy , Prostatic Neoplasms , Male , Prostatic Neoplasms/diagnostic imaging , Photothermal Therapy/methods , Humans , Animals , Mitochondria/metabolism , Mitochondria/drug effects , Cell Line, Tumor , Carbocyanines/chemistry , Optical Imaging/methods , Mice , Surgery, Computer-Assisted/methods , Fluorescent Dyes/chemistry , Mice, Nude , Mice, Inbred BALB C , Infrared Rays , Indocyanine Green/chemistry , Indocyanine Green/therapeutic use , Indocyanine Green/pharmacologyABSTRACT
An efficient single-dye NIR-II CL system was proposed for the first time with the longest emission peak around 1000 nm. Biocompatible CL nanoparticles were developed and a surprising CL intensity enhancement was found in the presence of the BASZn nanoenzyme by about three orders of magnitude. Such an NIR-II CL system was demonstrated for glucose sensing, tumor therapy and in vivo H2O2 imaging. Via theoretical and experimental analyses, a novel electron transfer model was established for such a chemiluminescence system rather than the generally considered HOMODye-LUMODOD model. These findings provide useful guidelines for designing efficient single-dye NIR-II CL systems.
