Cell-selective arrhythmia ablation for photomodulation of heart rhythm

Avula, Uma Mahesh R.; Yoon, Hyung Ki; Lee, Chang H.; Kaur, Kuljeet; Ramírez, Rafael J.; Takemoto, Yoshio; Ennis, Steven R.; Morady, Fred; Herron, Todd J.; Berenfeld, Omer; Kopelman, Raoul; Kalifa, Jérôme

doi:10.1126/scitranslmed.aab3665

Cited by 36 publications

(51 citation statements)

References 37 publications

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“…Herein, we report a photosensitizer-MnO 2 nanosystem assembled by the physisorption of the commonly used photosensitizer chlorin e6 (Ce6) on MnO 2 nanosheets for highly efficient PDT, 32-34 as shown in Scheme 1. In this design, MnO 2 nanosheets act as a nanocarrier for Ce6 and as an oxidant to reduce the level of intracellular GSH.…”

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confidence: 99%

A Smart Photosensitizer–Manganese Dioxide Nanosystem for Enhanced Photodynamic Therapy by Reducing Glutathione Levels in Cancer Cells

et al. 2016

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Photodynamic therapy (PDT) has been applied in cancer treatment by utilizing reactive oxygen species to kill cancer cells. However, a high concentration of Glutathione (GSH) is present in cancer cells and can consume reactive oxygen species. To address this problem, we report the development of a photosensitizer-MnO2 nanosystem for highly efficient PDT. In our design, MnO2 nanosheets adsorb photosensitizer chlorin e6 (Ce6), protect it from self-destruction upon light irradiation, and efficiently deliver it into cells. The nanosystem also inhibits extracellular singlet oxygen generation by Ce6, leading to fewer side effects. Once endocytosed, the MnO2 nanosheets are reduced by intracellular GSH. As a result, the nanosystem is disintegrated, simultaneously releasing Ce6 and decreasing the level of GSH for highly efficient PDT. Moreover, fluorescence recovery, accompanied by the dissolution of MnO2 nanosheets, can provide a fluorescence signal for monitoring the efficacy of delivery.

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confidence: 99%

A Smart Photosensitizer–Manganese Dioxide Nanosystem for Enhanced Photodynamic Therapy by Reducing Glutathione Levels in Cancer Cells

et al. 2016

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“…36 Previous in vivo studies indicate that F3 peptide modified nanoparticles show an increased retention time and target tumors significantly better than nontargeted nanopraticles. 34,35 The K + NS was surface modified with F3 peptide and fluorescence images were taken to monitor the uptake of the nanosensor by the cancer cells.…”

Section: Resultsmentioning

confidence: 99%

Ion-Selective Nanosensor for Photoacoustic and Fluorescence Imaging of Potassium

et al. 2017

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Ion-selective optodes (ISOs), the optical analog of ion-selective electrodes, have played an increasingly important role in chemical and biochemical analysis. Here we extend this technique to ion-selective photoacoustic optodes (ISPAOs) that serve at the same time as fluorescence-based ISOs, and apply it specifically to potassium (K+). Notably, the potassium ion is one of the most abundant cations in biological systems, involved in numerous physiological and pathological processes. Furthermore, it has been recently reported that the presence of abnormal extracellular potassium concentrations in tumors suppresses the immune responses and thus suppresses immunotherapy. However, unfortunately, sensors capable of providing potassium images in vivo are still a future proposition. Here, we prepared an ion-selective potassium nanosensor (NS) aimed at in vivo photoacoustic (PA) chemical imaging of the extracellular environment, while being also capable of fluorescence based intracellular ion-selective imaging. This potassium nanosensor (K+ NS) modulates its optical properties (absorbance and fluorescence) according to the potassium concentration. The K+ NS is capable of measuring potassium, in the range of 1 mM to 100 mM, with high sensitivity and selectivity, by ISPAO based measurements. Also, a near infrared dye surface modified K+ NS allows fluorescence-based potassium sensing in the range of 20 mM to 1 M. The K+ NS serves thus as both PA and fluorescence based nanosensor, with response across the biologically relevant K+ concentrations, from the extracellular 5 mM typical values (through PA imaging) to the intracellular 150 mM typical values (through fluorescence imaging).

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“…The results demonstrated the feasibility of cell specific photoablation, which might eventually become an alternative, or at least complementary therapy for rotor ablation using radiofrequency. (42)…”

Section: Rotor Formation and Substrate Related-stabilitymentioning

confidence: 99%

Structural and Functional Bases of Cardiac Fibrillation

Filgueiras‐Rama

Jalife

2016

JACC: Clinical Electrophysiology

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Evidence accumulated over the last 25 years suggests that, whether in the atria or ventricles, fibrillation may be explained by the self-organization of the cardiac electrical activity into rapidly spinning rotors giving way to spiral waves that break intermittently and result in fibrillatory conduction. The dynamics and frequency of such rotors depend on the ion channel composition, excitability and refractory properties of the tissues involved, as well as on the thickness and respective three-dimensional fiber structure of the atrial and ventricular chambers. Therefore, improving the understanding of fibrillation has required the use of multidisciplinary research approaches, including optical mapping, patch clamping and molecular biology, and the application of concepts derived from the theory of wave propagation in excitable media. Moreover, translation of such concepts to the clinic has recently opened new opportunities to apply novel mechanistic approaches to therapy, particularly during atrial fibrillation ablation. Here we review the current understanding of the manner in which the underlying myocardial structure and function influence rotor initiation and maintenance during cardiac fibrillation. We also examine relevant underlying differences and similarities between atrial fibrillation and ventricular fibrillation and evaluate the latest clinical mapping technologies used to identify rotors in either arrhythmia. Altogether, the data being discussed have significantly improved our understanding of the cellular and structural bases of cardiac fibrillation and pointed toward potentially exciting new avenues for more efficient and effective identification and therapy of the most complex cardiac arrhythmias.

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Cell-selective arrhythmia ablation for photomodulation of heart rhythm

Cited by 36 publications

References 37 publications

A Smart Photosensitizer–Manganese Dioxide Nanosystem for Enhanced Photodynamic Therapy by Reducing Glutathione Levels in Cancer Cells

A Smart Photosensitizer–Manganese Dioxide Nanosystem for Enhanced Photodynamic Therapy by Reducing Glutathione Levels in Cancer Cells

Ion-Selective Nanosensor for Photoacoustic and Fluorescence Imaging of Potassium

Structural and Functional Bases of Cardiac Fibrillation

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