Limits...
Molecular imaging of apoptosis: from micro to macro.

Zeng W, Wang X, Xu P, Liu G, Eden HS, Chen X - Theranostics (2015)

Bottom Line: Therefore strategies that enable visualized detection of apoptosis would be of enormous benefit in the clinic for diagnosis, patient management, and development of new therapies.In recent years, improved understanding of the apoptotic machinery and progress in imaging modalities have provided opportunities for researchers to formulate microscopic and macroscopic imaging strategies based on well-defined molecular markers and/or physiological features.Their clinical translation will also be our focus.

View Article: PubMed Central - PubMed

Affiliation: 1. School of Pharmaceutical Sciences, and Molecular Imaging Research Centre, Central South University, Changsha, 410013, China;

ABSTRACT
Apoptosis, or programmed cell death, is involved in numerous human conditions including neurodegenerative diseases, ischemic damage, autoimmune disorders and many types of cancer, and is often confused with other types of cell death. Therefore strategies that enable visualized detection of apoptosis would be of enormous benefit in the clinic for diagnosis, patient management, and development of new therapies. In recent years, improved understanding of the apoptotic machinery and progress in imaging modalities have provided opportunities for researchers to formulate microscopic and macroscopic imaging strategies based on well-defined molecular markers and/or physiological features. Correspondingly, a large collection of apoptosis imaging probes and approaches have been documented in preclinical and clinical studies. In this review, we mainly discuss microscopic imaging assays and macroscopic imaging probes, ranging in complexity from simple attachments of reporter moieties to proteins that interact with apoptotic biomarkers, to rationally designed probes that target biochemical changes. Their clinical translation will also be our focus.

Show MeSH

Related in: MedlinePlus

Real-time imaging of apoptosis with a polymeric nanoprobe. A) Schematic diagram of the caspase-3 activatable nanoprobe (Apo-NP). B) In vivo NIR fluorescence images of subcutaneous SCC7 tumor-bearing mice after intratumoral injection of the Apo-NP with or without pretreatment of doxorubicin (24 h before the probe injection). Only apoptotic tumors were clearly visualized. (Adapted from Ref. 158 with permission.)
© Copyright Policy
Related In: Results  -  Collection


getmorefigures.php?uid=PMC4377726&req=5

Figure 11: Real-time imaging of apoptosis with a polymeric nanoprobe. A) Schematic diagram of the caspase-3 activatable nanoprobe (Apo-NP). B) In vivo NIR fluorescence images of subcutaneous SCC7 tumor-bearing mice after intratumoral injection of the Apo-NP with or without pretreatment of doxorubicin (24 h before the probe injection). Only apoptotic tumors were clearly visualized. (Adapted from Ref. 158 with permission.)

Mentions: Because NP-based probes provide a platform for different quencher-fluorophore combinations such as multiple-to-one or multiple-to-multiple pairs, very recently, polymeric and inorganic NP-based activatable probes have been successfully developed. Lee et al. reported an activatable nanoprobe based on a polymer nanoparticle platform 158. This nanoprobe consists of strongly dual-quenched (dye-dark quencher and dye-dye quenching mechanisms), caspase-3-specific, and NIR fluorogenic peptides on the surface of hyaluronic acid-based, self-assembled polymeric nanoparticles (HA-NPs) that serve as carriers (Figure 11). The activatable nanoprobe can efficiently deliver dual-quenched caspase-3-sensitive fluorogenic peptides into cells, allowing caspase-3-dependent strong fluorescence amplification to be imaged in vitro and in vivo. To date, a large number of similar probes have been reported. However, few probes have been designed to target the caspase cascade during apoptosis. As a proof-of-concept, we described a simple one-step technique that enables real-time imaging of multiple intracellular caspase activities, which involves a straightforward peptide synthesis and a simple mixing step with a commercial transfection agent 159. The transfection agent efficiently delivered highly quenched fluorogenic probes, comprised of distinctive pairs of dyes and quenchers, to the initiator caspase-8 and the effector caspase-3 in apoptotic cells, allowing dual-imaging of the activities of both caspases during the apoptotic process. Furthermore, a set of protease specific substrates of the dye were conjugated on the reactive surface of a broad-spectrum nanoquencher, which was generated by incorporating 3-aminopropyltriethoxysilane (APS) conjugated to the individual dark quenchers BHQ-1, BHQ-2, and BHQ-3 (APS-BHQx), as well as the mixture of all three BHQs into mesoporous silica nanoparticles (MSNs) 160. The nanosensor is capable of producing multiplexed fluorescence signals in the presence of multiple proteases.


Molecular imaging of apoptosis: from micro to macro.

Zeng W, Wang X, Xu P, Liu G, Eden HS, Chen X - Theranostics (2015)

Real-time imaging of apoptosis with a polymeric nanoprobe. A) Schematic diagram of the caspase-3 activatable nanoprobe (Apo-NP). B) In vivo NIR fluorescence images of subcutaneous SCC7 tumor-bearing mice after intratumoral injection of the Apo-NP with or without pretreatment of doxorubicin (24 h before the probe injection). Only apoptotic tumors were clearly visualized. (Adapted from Ref. 158 with permission.)
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4377726&req=5

Figure 11: Real-time imaging of apoptosis with a polymeric nanoprobe. A) Schematic diagram of the caspase-3 activatable nanoprobe (Apo-NP). B) In vivo NIR fluorescence images of subcutaneous SCC7 tumor-bearing mice after intratumoral injection of the Apo-NP with or without pretreatment of doxorubicin (24 h before the probe injection). Only apoptotic tumors were clearly visualized. (Adapted from Ref. 158 with permission.)
Mentions: Because NP-based probes provide a platform for different quencher-fluorophore combinations such as multiple-to-one or multiple-to-multiple pairs, very recently, polymeric and inorganic NP-based activatable probes have been successfully developed. Lee et al. reported an activatable nanoprobe based on a polymer nanoparticle platform 158. This nanoprobe consists of strongly dual-quenched (dye-dark quencher and dye-dye quenching mechanisms), caspase-3-specific, and NIR fluorogenic peptides on the surface of hyaluronic acid-based, self-assembled polymeric nanoparticles (HA-NPs) that serve as carriers (Figure 11). The activatable nanoprobe can efficiently deliver dual-quenched caspase-3-sensitive fluorogenic peptides into cells, allowing caspase-3-dependent strong fluorescence amplification to be imaged in vitro and in vivo. To date, a large number of similar probes have been reported. However, few probes have been designed to target the caspase cascade during apoptosis. As a proof-of-concept, we described a simple one-step technique that enables real-time imaging of multiple intracellular caspase activities, which involves a straightforward peptide synthesis and a simple mixing step with a commercial transfection agent 159. The transfection agent efficiently delivered highly quenched fluorogenic probes, comprised of distinctive pairs of dyes and quenchers, to the initiator caspase-8 and the effector caspase-3 in apoptotic cells, allowing dual-imaging of the activities of both caspases during the apoptotic process. Furthermore, a set of protease specific substrates of the dye were conjugated on the reactive surface of a broad-spectrum nanoquencher, which was generated by incorporating 3-aminopropyltriethoxysilane (APS) conjugated to the individual dark quenchers BHQ-1, BHQ-2, and BHQ-3 (APS-BHQx), as well as the mixture of all three BHQs into mesoporous silica nanoparticles (MSNs) 160. The nanosensor is capable of producing multiplexed fluorescence signals in the presence of multiple proteases.

Bottom Line: Therefore strategies that enable visualized detection of apoptosis would be of enormous benefit in the clinic for diagnosis, patient management, and development of new therapies.In recent years, improved understanding of the apoptotic machinery and progress in imaging modalities have provided opportunities for researchers to formulate microscopic and macroscopic imaging strategies based on well-defined molecular markers and/or physiological features.Their clinical translation will also be our focus.

View Article: PubMed Central - PubMed

Affiliation: 1. School of Pharmaceutical Sciences, and Molecular Imaging Research Centre, Central South University, Changsha, 410013, China;

ABSTRACT
Apoptosis, or programmed cell death, is involved in numerous human conditions including neurodegenerative diseases, ischemic damage, autoimmune disorders and many types of cancer, and is often confused with other types of cell death. Therefore strategies that enable visualized detection of apoptosis would be of enormous benefit in the clinic for diagnosis, patient management, and development of new therapies. In recent years, improved understanding of the apoptotic machinery and progress in imaging modalities have provided opportunities for researchers to formulate microscopic and macroscopic imaging strategies based on well-defined molecular markers and/or physiological features. Correspondingly, a large collection of apoptosis imaging probes and approaches have been documented in preclinical and clinical studies. In this review, we mainly discuss microscopic imaging assays and macroscopic imaging probes, ranging in complexity from simple attachments of reporter moieties to proteins that interact with apoptotic biomarkers, to rationally designed probes that target biochemical changes. Their clinical translation will also be our focus.

Show MeSH
Related in: MedlinePlus