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Gold Nanoparticle-Based Fluorescent Theranostics for Real-Time Image-Guided Assessment of DNA Damage and Repair.

ABSTRACT: Chemotherapeutic dosing, is largely based on the tolerance levels of toxicity today. Molecular imaging strategies can be leveraged to quantify DNA cytotoxicity and thereby serve as a theranostic tool to improve the efficacy of treatments. Methoxyamine-modified cyanine-7 (Cy7MX) is a molecular probe which binds to apurinic/apyrimidinic (AP)-sites, inhibiting DNA-repair mechanisms implicated by cytotoxic chemotherapies. Herein, we loaded (Cy7MX) onto polyethylene glycol-coated gold nanoparticles (AuNP) to selectively and stably deliver the molecular probe intravenously to tumors. We optimized the properties of Cy7MX-loaded AuNPs using optical spectroscopy and tested the delivery mechanism and binding affinity using the DLD1 colon cancer cell line in vitro. A 10:1 ratio of Cy7MX-AuNPs demonstrated a strong AP site-specific binding and the cumulative release profile demonstrated 97% release within 12 min from a polar to a nonpolar environment. We further demonstrated targeted delivery using imaging and biodistribution studies in vivo in an xenografted mouse model. This work lays a foundation for the development of real-time molecular imaging techniques that are poised to yield quantitative measures of the efficacy and temporal profile of cytotoxic chemotherapies.

SUBMITTER: Srinivasan SS

PROVIDER: S-EPMC6387448 | biostudies-literature | 2019 Jan

REPOSITORIES: biostudies-literature

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Gold Nanoparticle-Based Fluorescent Theranostics for Real-Time Image-Guided Assessment of DNA Damage and Repair.

Srinivasan Shriya S SS Seenivasan Rajesh R Condie Allison A Gerson Stanton L SL Wang Yanming Y Burda Clemens C

International journal of molecular sciences 20190122 3

Chemotherapeutic dosing, is largely based on the tolerance levels of toxicity today. Molecular imaging strategies can be leveraged to quantify DNA cytotoxicity and thereby serve as a theranostic tool to improve the efficacy of treatments. Methoxyamine-modified cyanine-7 (Cy7MX) is a molecular probe which binds to apurinic/apyrimidinic (AP)-sites, inhibiting DNA-repair mechanisms implicated by cytotoxic chemotherapies. Herein, we loaded (Cy7MX) onto polyethylene glycol-coated gold nanoparticles ( ...[more]

PMID: 30678294

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Project description:Rationale: High-intensity focused ultrasound (HIFU) therapy represents a noninvasive surgical approach to treat uterine fibroids. The operation of HIFU therapy relies on the information provided by medical images. In current HIFU therapy, all operations such as positioning of the lesion in magnetic resonance (MR) and ultrasound (US) images are manually performed by specifically trained doctors. Manual processing is an important limitation of the efficiency of HIFU therapy. In this paper, we aim to provide an automatic and accurate image guidance system, intelligent diagnosis, and treatment strategy for HIFU therapy by combining multimodality information. Methods: In intelligent HIFU therapy, medical information and treatment strategy are automatically processed and generated by a real-time image guidance system. The system comprises a novel multistage deep convolutional neural network for preoperative diagnosis and a nonrigid US lesion tracking procedure for HIFU intraoperative image-assisted treatment. In the process of intelligent therapy, the treatment area is determined from the autogenerated lesion area. Based on the autodetected treatment area, the HIFU foci are distributed automatically according to the treatment strategy. Moreover, an image-based unexpected movement warning and other physiological monitoring are used during the intelligent treatment procedure for safety assurance. Results: In the experiment, we integrated the intelligent treatment system on a commercial HIFU treatment device, and eight clinical experiments were performed. In the clinical validation, eight randomly selected clinical cases were used to verify the feasibility of the system. The results of the quantitative experiment indicated that our intelligent system met the HIFU clinical tracking accuracy and speed requirements. Moreover, the results of simulated repeated experiments confirmed that the autodistributed HIFU focus reached the level of intermediate clinical doctors. Operations performed by junior- or middle-level operators with the assistance of the proposed system can reach the level of operation performed by senior doctors. Various experiments prove that our proposed intelligent HIFU therapy process is feasible for treating common uterine fibroid cases. Conclusion: We propose an intelligent HIFU therapy for uterine fibroid which integrates multiple medical information processing procedures. The experiment results demonstrated that the proposed procedures and methods can achieve monitored and automatic HIFU diagnosis and treatment. This research provides a possibility for intelligent and automatic noninvasive therapy for uterine fibroid.

Dataset Information

Gold Nanoparticle-Based Fluorescent Theranostics for Real-Time Image-Guided Assessment of DNA Damage and Repair.

Publications

Gold Nanoparticle-Based Fluorescent Theranostics for Real-Time Image-Guided Assessment of DNA Damage and Repair.

Similar Datasets

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