Polydopamine decorated tobacco mosaic theranostic virus nanoparticles
Inventors
Assignees
Case Western Reserve University
Publication Number
US-12239721-B2
Publication Date
2025-03-04
Expiration Date
2040-12-21
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Abstract
A nanoparticle for diagnostic, therapeutic, and/or theranostic applications includes a rod-shaped plant virus like particle (VLP), one or more gadolinium T1 contrast agents conjugated to an interior surface of the VLP, and a layer of polydopamine (PDA) coated over a portion of the exterior surface of the VLP.
Core Innovation
The invention provides a nanoparticle composed of a rod-shaped plant virus-like particle (VLP), with one or more gadolinium T1 contrast agents conjugated to its interior surface and a layer of polydopamine (PDA) coating a portion of its exterior surface. The VLP is preferably from the Virgaviridae family, such as the tobacco mosaic virus (TMV), and offers a platform for simultaneous diagnostic, therapeutic, and theranostic applications, including multimodal imaging and photothermal therapy (PTT).
The problem addressed relates to the limitations of existing nanocarrier platforms and MRI contrast agents in biomedical applications. Conventional gadolinium-based MRI agents suffer from poor longitudinal relaxivity (r1), especially at higher magnetic field strengths, reducing their effectiveness in clinical imaging. Additionally, stable, biocompatible delivery vehicles for targeted tissue imaging and therapy that avoid aggregation and are suitable for multimodal use are needed.
By combining gadolinium contrast agents inside a virally derived, rod-shaped VLP and coating it partially with polydopamine, the nanoparticle achieves enhanced imaging (MRI and photoacoustic) properties, increases relaxivity, prevents aggregation, and enables efficient photothermal conversion for therapy. The PDA coating is applied via in situ self-polymerization and the resultant particles can be tailored for use in cancer imaging and treatment, offering dual or multi-modal diagnostic and therapeutic capabilities.
Claims Coverage
There are two independent claims that define the main inventive features of this patent.
Nanoparticle comprising a rod-shaped plant VLP with interior gadolinium contrast agent conjugation and exterior polydopamine coating
A nanoparticle containing: - A rod-shaped plant virus like particle (VLP). - One or more gadolinium contrast agents conjugated to the interior surface of the VLP. - A layer of polydopamine (PDA) coated over a portion of the exterior surface of the VLP. - The nanoparticle is formulated such that the amount of PDA is effective to inhibit aggregation with additional PDA-coated VLPs.
Method for detecting and/or treating cancer using PDA-coated gadolinium-conjugated VLPs
A method comprising: 1. Administering to a subject a plurality of nanoparticles, each comprising— - A rod-shaped plant virus like particle (VLP), - One or more gadolinium contrast agents conjugated to interior surfaces of the VLPs, and - Layers of polydopamine (PDA) coated over a portion of the exterior surfaces, with the PDA amount effective to inhibit aggregation. 2. Detecting the nanoparticles in the subject using one or more imaging devices after administration to determine location and/or distribution of cancer. 3. Optionally delivering photothermal therapy (PTT) to the VLPs at the location of the cancer in the subject.
The inventive features focus on the specific assembly of a rod-shaped plant virus-like nanoparticle with interior gadolinium conjugation and a partial PDA coating that inhibits aggregation, along with their application in cancer detection and treatment using imaging and optional photothermal therapy.
Stated Advantages
Biocompatible and biodegradable plant VLPs do not infect humans or mammals and can be produced simply and inexpensively.
Polydopamine coating increases longitudinal relaxivity (r1) of gadolinium contrast agents, especially at high magnetic fields, enhancing MRI sensitivity.
Particles exhibit high photothermal conversion efficiency and photothermal stability for effective photothermal therapy.
Formulation enables dual or multi-modal imaging capabilities, notably MRI and photoacoustic imaging, for improved localization and monitoring.
PDA coating prevents aggregation of nanoparticles, maintaining dispersion and functional performance.
Nanoparticles are preferentially internalized by cancer cells, supporting targeted therapy and increasing therapeutic efficiency.
Documented Applications
Detection and imaging of cancer (including breast cancer and prostate cancer) in a subject using MRI and/or photoacoustic imaging.
Treatment of cancer in a subject by photothermal therapy (PTT) following nanoparticle accumulation at the cancer site.
Method of targeting diseased tissue, such as cancer tissue, with PDA-coated rod-shaped plant VLPs loaded with gadolinium contrast agents.
Use as theranostic agents combining diagnostic imaging and therapeutic functions for cancer in mammalian or human subjects.
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