Cell-Permeable and Biocompatible Polymeric Nanoparticles for Apoptosis Imaging

Kim, Kwangmeyung; Lee, Misu; Park, Hyungkyu; Kim, Jong Ho; Kim, Sung-Won; Chung, Heesun; Choi, Kuiwon; Kim, In San; Seong, Baik Lin; Kwon, Ick Chan

doi:10.1021/ja057712f

Cited by 230 publications

(169 citation statements)

References 6 publications

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“…Cell-permeable polymeric nanoparticles have also been prepared for apoptosis imaging. The close spatial proximity of the near-infrared fluorochromes in polymeric nanoparticles resulted in an autoquenched state and strong near-infrared fluorescence signal emitted in apoptotic cells (20). Theranostic agents that combine therapeutic components and a caspase-activatable imaging moiety have also been reported (21).…”

Section: Activatable Probes For Caspasesmentioning

confidence: 99%

Apoptosis Imaging: Beyond Annexin V

2010

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Induction of apoptosis is the primary mechanism through which most chemotherapies cause tumor cell death. Early assessment of tumor response is required to manage patients in terms of quality of life versus intensive chemotherapy. Although imaging with radiolabeled annexin V has been intensively investigated, it is still not sufficiently mature for clinical application. This article will summarize various alternative imaging techniques for visualization of phosphatidylserine externalization, activity of caspases, and mitochondrial membrane potential. Such imaging studies will promote the identification of novel molecular targets and the development of highly specific apoptosis-detecting imaging probes with potential clinical applications. It is highly possible that quantitative imaging of apoptosis will greatly improve clinical decision making in apoptosis-related diseases.

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Section: Activatable Probes For Caspasesmentioning

confidence: 99%

Apoptosis Imaging: Beyond Annexin V

2010

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“…Several synthetic activatable probes have been developed to image caspase-3 activity directly, but most of these probes suffer from low cell membrane penetration and relatively high background due to the nonspecific cleavage (18,19). Consequently, fluorescence and bioluminescence reporter systems have been developed based on a small peptide aspartylglutamylvalanyl aspartic acid (DEVD), which can be recognized and cleaved by caspase-3 (17,(20)(21)(22). Although optical imaging with these reporter probes has been demonstrated to be useful for in vivo monitoring of apoptosis especially in cell culture or s.c. animal models (23)(24)(25)(26)(27)(28), further applications of these approaches are thwarted by tissue attenuation of photons and lack of fully quantitative and tomographic capabilities.…”

mentioning

confidence: 99%

A cyclic HSV1-TK reporter for real-time PET imaging of apoptosis

Wang

Hida

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

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The coordination of cell proliferation and programmed death (apoptosis) is essential for normal physiology, and imbalance in these two opposing processes is implicated in various diseases. Objective and quantitative noninvasive imaging of apoptosis would significantly facilitate rapid screening as well as validation of therapeutic chemicals. Herein, we molecularly engineered an apoptosis switch-on PET-based cyclic herpes simplex virus type 1-thymidine kinase reporter (cTK266) containing a caspase-3 recognition domain as the switch. Translation of the reporter and protein splicing in healthy mammalian cells produce an inactive cyclic chimera. Upon apoptosis, caspase-3-specific cleavage of the circular product occurs, resulting in the restoration of the thymidine kinase activity, which can be detected in living cells and animals by noninvasive PET imaging. Our results showed the high sensitivity of this reporter in dynamic and quantitative imaging of apoptosis in living subjects. This reporter could be applied as a valuable tool for high-throughput functional screening of proapoptotic and antiapoptotic compounds in preclinical models in drug development, and monitoring the destination of therapeutic cells in clinical settings.reporter probe | positron-emission tomography

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“…Similarly, a cell-penetrating TcapQ was recently developed to improve the pharmacokinetic properties and improve delivery of FRET-based caspase probes (68). Additionally, nanoparticles have been used to detect caspase activity (69,70). Separately, nanoparticles have been used previously to deliver paclitaxel or other cytotoxic agents (71).…”

Section: Discussionmentioning

confidence: 99%

Reporter nanoparticle that monitors its anticancer efficacy in real time

Kulkarni

Rao

Natarajan

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

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The ability to monitor the efficacy of an anticancer treatment in real time can have a critical effect on the outcome. Currently, clinical readouts of efficacy rely on indirect or anatomic measurements, which occur over prolonged time scales postchemotherapy or postimmunotherapy and may not be concordant with the actual effect. Here we describe the biology-inspired engineering of a simple 2-in-1 reporter nanoparticle that not only delivers a cytotoxic or an immunotherapy payload to the tumor but also reports back on the efficacy in real time. The reporter nanoparticles are engineered from a novel two-staged stimuli-responsive polymeric material with an optimal ratio of an enzyme-cleavable drug or immunotherapy (effector elements) and a drug function-activatable reporter element. The spatiotemporally constrained delivery of the effector and the reporter elements in a single nanoparticle produces maximum signal enhancement due to the availability of the reporter element in the same cell as the drug, thereby effectively capturing the temporal apoptosis process. Using chemotherapy-sensitive and chemotherapy-resistant tumors in vivo, we show that the reporter nanoparticles can provide a real-time noninvasive readout of tumor response to chemotherapy. The reporter nanoparticle can also monitor the efficacy of immune checkpoint inhibition in melanoma. The self-reporting capability, for the first time to our knowledge, captures an anticancer nanoparticle in action in vivo.T he failure of anticancer therapy is a major cause of mortality (1). Although the current dogma underlying resistance is based on the Darwinian selection of mutations acquired over time under chemotherapy pressure, emerging evidence indicates that anticancer drugs can be rendered ineffective early on by intrinsic or adaptive resistance as a function of tumor heterogeneity (2-4). For example, response rates to first-line chemotherapy treatments in metastatic breast cancer patients range from a dismal 30% to 70%, and patients with disease progression need to be switched to a different drug (5). Similarly, about 40-60% of patients with a wild-type KRAS do not respond to cetuximab (6). The ability to detect early whether a treatment is working or not and to switch, if necessary, to a regimen that is effective can have a significant effect on the outcome as well as quality of life (7,8).Currently, tumor response to therapy is determined using techniques for direct anatomical measurements, such as computed tomography (CT) and magnetic resonance imaging, or indirectly using positron emission tomography with 2-[fluorine-18]fluoro-2-deoxy-d-glucose (FDG-PET) to quantify metabolic activity. However, these techniques lack the sensitivity or specificity to enable very early response assessment, and often, clinicopathological and metabolic readouts can be discordant (5, 9, 10). In the case of immunotherapy, for example, a productive immune response (T cell infiltration) and the unimpeded growth of the tumor will both be manifest as progression on the conventional ...

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Cell-Permeable and Biocompatible Polymeric Nanoparticles for Apoptosis Imaging

Cited by 230 publications

References 6 publications

Apoptosis Imaging: Beyond Annexin V

Apoptosis Imaging: Beyond Annexin V

A cyclic HSV1-TK reporter for real-time PET imaging of apoptosis

Reporter nanoparticle that monitors its anticancer efficacy in real time

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