Ultrasound-responsive theranostic platform for real-time monitoring and efficient thrombolysis in tPA-resistant thrombi
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ABSTRACT:
PROVIDER: PRJNA1071989 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR27830211_1.fastq.gz | Fastqsanger.gz | |||
| SRR27830211_2.fastq.gz | Fastqsanger.gz | |||
| SRR27830212_1.fastq.gz | Fastqsanger.gz | |||
| SRR27830212_2.fastq.gz | Fastqsanger.gz | |||
| SRR27830213_1.fastq.gz | Fastqsanger.gz |
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Project description:There is no effective and noninvasive solution for thrombolysis because the mechanism by which certain thrombi become tissue plasminogen activator (tPA)-resistant remains obscure. Endovascular thrombectomy is the last option for these tPA-resistant thrombi, thus a new noninvasive strategy is urgently needed. Through an examination of thrombi retrieved from stroke patients, we found that neutrophil extracellular traps (NETs), ε-(γ-glutamyl) lysine isopeptide bonds and fibrin scaffolds jointly comprise the key chain in tPA resistance. A theranostic platform is designed to combine sonodynamic and mechanical thrombolysis under the guidance of ultrasonic imaging. Breakdown of the key chain leads to a recanalization rate of more than 90% in male rat tPA-resistant occlusion model. Vascular reconstruction is observed one month after recanalization, during which there was no thrombosis recurrence. The system also demonstrates noninvasive theranostic capabilities in managing pigs' long thrombi (>8 mm) and in revascularizing thrombosis-susceptible tissue-engineered vascular grafts, indicating its potential for clinical application. Overall, this noninvasive theranostic platform provides a new strategy for treating tPA-resistant thrombi.
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Project description:Intravenous thrombolysis possesses critical defects in efficiency and post-thrombolysis hemorrhage due to the current empirical body weight-based medication strategy. However, the inherent heterogeneity of thrombi, instead of body weight, endows thrombi different thrombolysis resistance and affect the thrombolytic outcome. The lack of methods for perceiving thrombolysis resistance has severely hindered the precise medication of vascular embolization. Here, we described the relationship between the thrombin heterogeneity in thrombi and the thrombolysis resistance of thrombi, and created an artificial biomarker-based nano-patrol system to perceive and report the thrombolysis resistance of thrombi taking advantage of the specific recognition and allosteric ability of aptamer-based DNA structure. The nano-patrols are able to accomplish thrombolysis resistance-matched personalized precise therapy through the NIR-Ⅱ laser-regulated synergistic thrombolytic effect, according to the feedback signal from artificial biomarkers. This new strategy depicted enhanced thrombolytic efficiency than alteplase for rats, mini pigs and clinical thrombi, achieved recanalization in thrombotic model where alteplase encountered failure. Moreover, the nano-patrol system remarkably reduced the infarct volume and the hemorrhagic transformation risk (0.12-fold of alteplase) of cerebral thrombosis. This nano-patrol system developed new tool for the assessment of thrombolysis resistance and personalized precise thrombolysis with lower hemorrhagic risk.
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Project description:Echo-contrast agents enhance the echogenicity of ultrasound and have been clinically used for diagonosis in current medical fields. Here, the combined effects of Sonazoid, an echo-contrast agent, and ultrasound on the gene expression in human lymphoma U937 cells were investigated using an Affymetrix GeneChip system. The cells were treated with Sonazoid (0.05%; Sonazoid only), ultrasound (0.3 W/cm2 for 1 min; ultrasound only) and the combination of Sonazoid and ultrasound (0.05% Sonazoid plus ultrasound 0.3 W/cm2 for 1 min; Sonazoid + Ultrasound) and followed by incubation for 3 h at 37°C. The percentage of DNA fragmentation 6 h after treatment was 5.8 ± 1.0 (mean ± SD, n = 3), 6.0 ± 0.4, 13.5 ± 1.0, and 18.3 ± 2.3 in cells treated with control, Sonazoid only, ultrasound only and Sonazoid + Ultrasound, respectively. Of approximately 47,000 probe sets analyzed, probe sets that were differentially expressed by a factor 2.0 or greater were 40, 184 and 144 in cells treated with Sonazoid only, ultrasound only and Sonazoid + Ultrasound, respectively.
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