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Magnetic lipid nanovehicles synergize the controlled thermal release of chemotherapeutics with magnetic ablation while enabling non-invasive monitoring by MRI for melanoma theranostics.

ABSTRACT: Nowadays, a number of promising strategies are being developed that aim at combining diagnostic and therapeutic capabilities into clinically effective formulations. Thus, the combination of a modified release provided by an organic encapsulation and the intrinsic physico-chemical properties from an inorganic counterpart opens new perspectives in biomedical applications. Herein, a biocompatible magnetic lipid nanocomposite vehicle was developed through an efficient, green and simple method to simultaneously incorporate magnetic nanoparticles and an anticancer drug (doxorubicin) into a natural nano-matrix. The theranostic performance of the final magnetic formulation was validated in vitro and in vivo, in melanoma tumors. The systemic administration of the proposed magnetic hybrid nanocomposite carrier enhanced anti-tumoral activity through a synergistic combination of magnetic hyperthermia effects and antimitotic therapy, together with MRI reporting capability. The application of an alternating magnetic field was found to play a dual role, (i) acting as an extra layer of control (remote, on-demand) over the chemotherapy release and (ii) inducing a local thermal ablation of tumor cells. This combination of chemotherapy with thermotherapy establishes a synergistic platform for the treatment of solid malignant tumors under lower drug dosing schemes, which may realize the dual goal of reduced systemic toxicity and enhanced anti-tumoral efficacy.

SUBMITTER: Garcia-Hevia L

PROVIDER: S-EPMC8424388 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:This work explored an elementwise approach to model transcranial MRI-guided focused ultrasound (TcMRgFUS) thermal ablation, a noninvasive approach to neurosurgery. Each element of the phased array transducer was simulated individually and could be simultaneously loaded into computer memory, allowing for rapid (~2.5 s) calculation of the pressure field for different phase offsets used for beam steering and aberration correction. We simulated the pressure distribution for 431 sonications in 32 patients, applied the phase and magnitude values used during treatment, and estimated the resulting temperature rise. We systematically varied the relationship between CT (computerized tomography)-derived skull density and the acoustic attenuation and sound speed to obtain the best agreement between the predictions and MR temperature imaging (MRTI). The optimization was validated with simulations of 396 sonications from 40 additional treatments. After optimization, the predicted and measured heating agreed well (R2: 0.74 patients 1-32; 0.71 patients 33-72). The dimensions and obliquity of the heating in the simulated temperature maps were correlated with the MRTI (R2: 0.62, 0.74, respectively), but the measured heating was more spatially diffuse. The energy needed to achieve ablation varied by an order of magnitude (3.3-36.1 kJ). While this elementwise approach required more computation time up front (the combined simulation matrices were approximately 4.6 times higher than a single large simulation), it could be performed in parallel on a computing cluster. It allows for rapid calculation of the three-dimensional heating at the focus for different phase and magnitude values on the array. We also show how this approach can be used to optimize the relationship between CT-derived skull density and acoustic properties. While the relationships found here need further validation in a larger patient population, these results demonstrate the promise of this approach to model TcMRgFUS.

Project description:Introduction: Growing advances in nanotechnology have facilitated the applications of newly emerged nanomaterials in the field of biomedical/pharmaceutical sciences. Following this trend, the multifunctional nanoparticles (NPs) play a significant role in development of advanced drug delivery systems (DDSs) such as diapeutics/theranostics used for simultaneous diagnosis and therapy. Multifunctional radiolabeled NPs with capability of detecting, visualizing and destroying diseased cells with least side effects have been considered as an emerging filed in presentation of the best choice in solving the therapeutic problems. Functionalized magnetic and gold NPs (MNPs and GNPs, respectively) have produced the potential of nanoparticles as sensitive multifunctional probes for molecular imaging, photothermal therapy and drug delivery and targeting. Methods: In this study, we review the most recent works on the improvement of various techniques for development of radiolabeled magnetic and gold nanoprobes, and discuss the methods for targeted imaging and therapies. Results: The receptor-specific radiopharmaceuticals have been developed to localized radiotherapy in disease sites. Application of advanced multimodal imaging methods and related modality imaging agents labeled with various radioisotopes (e.g., 125I, 111In, 64Cu, 68Ga, 99mTc) and MNPs/GNPs have significant effects on treatment and prognosis of cancer therapy. In addition, the surface modification with biocompatible polymer such as polyethylene glycol (PEG) have resulted in development of stealth NPs that can evade the opsonization and immune clearance. These long-circulating agents can be decorated with homing agents as well as radioisotopes for targeted imaging and therapy purposes. Conclusion: The modified MNPs or GNPs have wide applications in concurrent diagnosis and therapy of various malignancies. Once armed with radioisotopes, these nanosystems (NSs) can be exploited for combined multimodality imaging with photothermal/photodynamic therapy while delivering the loaded drugs or genes to the targeted cells/tissues. These NSs will be a game changer in combating various cancers.

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Magnetic lipid nanovehicles synergize the controlled thermal release of chemotherapeutics with magnetic ablation while enabling non-invasive monitoring by MRI for melanoma theranostics.

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