A Renal‐Clearable Activatable Molecular Probe for Fluoro‐Photacoustic and Radioactive Imaging of Cancer Biomarkers

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Early evaluation and prediction of the radiotherapy effect against tumors are crucial for effective radiotherapy management. The clinical approach generally relies on anatomical changes in tumor size, which is unable to promptly reflect clinical outcomes and guide a timely adjustment of therapy regimens. To resolve it, we herein develop a self-assembled organic probe (dCyFFs) with caspase-3 (Casp-3)-activatable near-infrared (NIR) fluoro-photoacoustic signals for early evaluation and prediction of radiotherapy efficacy. The probe contains an NIR dye that is caged with a Casp-3-cleavable substrate and linked to a self-assembly initiating moiety. In the presence of Casp-3, the self-assembled probe can undergo secondary assembly into larger nanoparticles and simultaneously activate NIR fluoro-photoacoustic signals. Such a design endows a superior real-time longitudinal imaging capability of Casp-3 generated by radiotherapy as it facilitates the passive accumulation of the probe into tumors, activated signal output with enhanced optical stability, and retention capacity relative to a nonassembling small molecular control probe (dCy). As a result, the probe enables precise prediction of the radiotherapy effect as early as 3 h posttherapy, which is further evidenced by the changes in tumor size after radiotherapy. Overall, the probe with Casp-3-mediated secondary assembly along with activatable NIR fluoro-photoacoustic signals holds great potential for evaluating and predicting the response of radiotherapy in a timely manner, which can also be explored for utilization in other therapeutic modalities.

Section: Introductionmentioning

confidence: 99%

A Self-Assembled Organic Probe with Activatable Near-Infrared Fluoro-Photoacoustic Signals for In Vivo Evaluation of the Radiotherapy Effect

An,

Gu,

Miao

et al. 2023

Self Cite

“…Therefore, we rationally developed a tumor-targeted FL/PA probe for Caspase-3-responsive imaging of tumor apoptosis. As shown in Figure , the tumor-targeted FL/PA probe ( Bio-DEVD-HCy) can be divided into three parts: (1) the biotin part for tumor targeting; , (2) the peptide part Asp-Glu-Val-Asp (DEVD) for specific Caspase-3 cleavage; , (3) the hemicyanine dye (HCy) part with outstanding near-infrared (NIR) optical property for responsive FL/PA imaging. − The FL/PA signal is “off” due to the caged amino group of HCy inhibiting intramolecular charge transfer (ICT) in Bio-DEVD-HCy . Once tumor cells are encountered, Bio-DEVD-HCy binds to the highly expressed biotin receptor on the surface and then enters and accumulates in tumor cells.…”

mentioning

confidence: 99%

Caspase-3-Responsive Fluorescent/Photoacoustic Imaging of Tumor Apoptosis

Liu

Wang

et al. 2023

Caspase-3 is an essential executor in apoptosis, and its activation has been regarded as a biomarker of cell apoptosis. The development of Caspase-3-responsive multimodal probes is a promising research prospect. Fluorescent/photoacoustic (FL/PA) imaging has attracted considerable attention due to the high sensitivity of FL as well as the high spatial resolution and penetration depth of PA. To our knowledge, there has been no tumor-targeted FL/PA probe to monitor the activity of Caspase-3 in vivo. Therefore, we developed a tumor-targeted FL/PA probe (Bio-DEVD-HCy) for Caspase-3-responsive imaging of tumor apoptosis. Ac-DEVD-HCy without tumor-targeted biotin is used as a control probe. In vitro experiments indicated that Bio-DEVD-HCy is superior to Ac-DEVD-HCy because of the higher kinetic parameter of Bio-DEVD-HCy in comparison to Ac-DEVD-HCy. Cell and tumor imaging results suggested that Bio-DEVD-HCy could enter and accumulate in tumor cells with higher FL/PA signal with the help of tumor-targeted biotin. In detail, Bio-DEVD-HCy or Ac-DEVD-HCy could image apoptotic tumor cells with 4.3-fold or 3.5-fold FL enhancement and 3.4-fold or 1.5-fold PA enhancement. Bio-DEVD-HCy or Ac-DEVD-HCy could image tumor apoptosis with 2.5-fold or 1.6-fold FL enhancement and 4.1-fold or 1.9-fold PA enhancement. We envision that Bio-DEVD-HCy will be applied for FL/PA imaging of tumor apoptosis in clinical settings.

“…Therefore, we rationally designed a tumor-targeted FL/PA probe for β-gal-activatable imaging of tumor senescence. As shown in Figure , the tumor-targeted FL/PA probe ( Gal-HCy-Biotin ) consists of three parts: (1) β-D-galactose is the specific substrate for β-gal; , (2) hemicyanine dye (HCy) with excellent near-infrared (NIR) optical property is the signal source for responsive FL/PA imaging; − (3) biotin is for tumor targeting due to the abundant biotin receptor in tumor cells. − Since the hydroxyl group of HCy in Gal-HCy-Biotin was caged, it has quenched FL/PA signal with inhibited intramolecular charge transfer (ICT). Gal-HCy-Biotin can enter and accumulate in tumor cells by binding to the overexpressed biotin receptor on the surface.…”

mentioning

confidence: 99%

β-Galactosidase-Activatable Fluorescent and Photoacoustic Imaging of Tumor Senescence

Liu

Tao

et al. 2023

β-Galactosidase (β-gal) is the gold standard marker of cellular senescence, which is linked with various age-related diseases. Therefore, it is essential to develop more excellent probes that can realtime monitor β-gal activity in cellular senescence in vivo. Fluorescent/ photoacoustic (FL/PA) dual-modal imaging possesses excellent sensitivity and spatial resolution. To our knowledge, there has been no tumor-targeted FL/PA probe to image cellular senescence by monitoring the activity of β-gal in vivo. Therefore, we developed a tumor-targeted FL/PA probe (Gal-HCy-Biotin) for β-gal-activatable imaging of tumor senescence. Gal-HCy without tumor-targeted biotin is used as a control probe. Gal-HCy-Biotin is superior to Gal-HCy due to the higher kinetic parameter of Gal-HCy-Biotin than Gal-HCy in vitro. Moreover, biotin could help Gal-HCy-Biotin enter and accumulate in tumor cells with higher FL/PA signal. In detail, Gal-HCy-Biotin or Gal-HCy could image senescent tumor cells with 4.6-fold or 3.5fold FL enhancement and 4.1-fold or 3.3-fold PA enhancement. Gal-HCy-Biotin or Gal-HCy could image tumor senescence with 2.9-fold or 1.7-fold FL enhancement and 3.8-fold or 1.3-fold PA enhancement. We envision that Gal-HCy-Biotin will be applied for FL/PA imaging of tumor senescence in clinic.