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Photoacoustic imaging (PAI) is an emerging analytical modality that is under intense preclinical development for the early diagnosis of various medical conditions, including cancer. However, the lack of specific tumor targeting by various contrast agents used in PAI obstructs its clinical applications. In this study, we developed indocyanine green (ICG)-encapsulated micelles specific for the CD 44 receptor and used in near infrared and photoacoustic imaging of tumors. ICG was hydrophobically modified prior to loading into hyaluronic acid (HA)-based micelles utilized for CD 44 based-targeting. We investigated the physicochemical characteristics of prepared HA only and ICG-encapsulated HA micelles (HA-ICG micelles). After intravenous injection of tumor-bearing mice, the bio-distribution and in vivo photoacoustic images of ICG-encapsulated HA micelles accumulating in tumors were also investigated. Our study further encourages the application of this HA-ICG-based nano-platform as a tumor-specific contrast agent for PAI.

In a previous study, we developed an E1 monobody specific for the tumor biomarker hEphA2 [PLoS ONE (2015) 10(7): e0132976]. E1 showed potential as a molecular probe for in vitro and in vivo targeting of cancers overexpressing hEphA2. In the present study, we constructed expression vectors for E1 conjugated to optical reporters such as Renilla luciferase variant 8 (Rluc8) or enhanced green fluorescent protein (EGFP) and purified such recombinant proteins by affinity chromatography in E. coli. E1-Rluc8 and E1-EGFP specifically bound to hEphA2 in human prostate cancer PC3 cells but not in human cervical cancer HeLa cells, which express hEphA2 at high and low levels, respectively. These recombinant proteins maintained >40% activity in mouse serum at 24 h. In vivo optical imaging for 24 h did not detect E1-EGFP signals, whereas E1-Rluc8 showed tumor-specific luminescence signals in PC3 but not in HeLa xenograft mice. E1-Rluc8 signals were detected at 4 h, peaked at 12 h, and were undetectable at 24 h. These results suggest the potential of E1-Rluc8 as an EphA2-specific optical imaging agent.