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

Abstract

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.

Selenadiazole-Induced Hela Cell Apoptosis through the Redox Oxygen Species-Mediated JAK2/STAT3 Signaling Pathway

“…The levels of mitochondrial apoptosis-related proteins, Bcl-2, and caspase-9 decreased or increased following the increasing doses of selenadiazole, respectively (Figure ). Additionally, the critical protein of apoptosis, caspase-3, increased as the concentration of selenadiazole rose. , Collectively, we can clue that selenadiazole triggered impaired mitochondria and activated caspase-9-mediated mitochondrial apoptosis. It is worth noting that how selenadiazole causes caspase-9-mediated mitochondrial apoptosis remained unresolved.…”

Activity-Based Fluorescence Diagnostics for Cancer

“…In addition to those highlighted here, other fluorescence probes targeting different biomarkers or fluorescence probes based on different detection mechanisms such as aggregation-induced emission (AIE) , and excited-state intramolecular proton transfer (ESIPT) , have been also developed. Moreover, activatable probes based on other technologies such as chemiluminescence, − photoacoustic imaging ,− and Raman imaging , have been reported in recent years. More sophisticated contrast probes utilizing these technologies can be anticipated.…”

Caspase-3-Responsive, Fluorogenic Bivalent Bottlebrush Polymers

“…Harnessing the ability of enzymes to trigger responses in polymeric materials facilitates the design of targeted therapeutics, imaging agents, and assemblies. − Caspase-3 (CASP3), a useful enzyme for such applications, is an executioner cysteine protease that cleaves the amide bond in the last aspartate residue of Asp–X a –X b –Asp peptide sequences, where X a is a hydrophobic amino acid such as valine and X b is a hydrophilic amino acid such as glutamic acid . Chemical tools for measuring CASP3 activity in disease microenvironments, e.g., by leveraging its ability to selectively activate imaging agents bound to polymeric particles through CASP3-cleavable peptides, can provide convenient, noninvasive imaging of therapeutic efficacy. − On the other hand, measuring the rates of change in CASP3-induced image signals as a function of cleavable peptide location within a complex synthetic polymer architecture could provide a way to measure CASP3 access to such materials, guiding the design of next-generation protease-responsive nanomaterials.…”