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Viral nanoparticles for drug delivery, imaging, immunotherapy, and theranostic applications.

ABSTRACT: Viral nanoparticles (VNPs) encompass a diverse array of naturally occurring nanomaterials derived from plant viruses, bacteriophages, and mammalian viruses. The application and development of VNPs and their genome-free versions, the virus-like particles (VLPs), for nanomedicine is a rapidly growing. VLPs can encapsulate a wide range of active ingredients as well as be genetically or chemically conjugated to targeting ligands to achieve tissue specificity. VLPs are manufactured through scalable fermentation or molecular farming, and the materials are biocompatible and biodegradable. These properties have led to a wide range of applications, including cancer therapies, immunotherapies, vaccines, antimicrobial therapies, cardiovascular therapies, gene therapies, as well as imaging and theranostics. The use of VLPs as drug delivery agents is evolving, and sufficient research must continuously be undertaken to translate these therapies to the clinic. This review highlights some of the novel research efforts currently underway in the VNP drug delivery field in achieving this greater goal.

SUBMITTER: Chung YH

PROVIDER: S-EPMC7320870 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Viral nanoparticles for drug delivery, imaging, immunotherapy, and theranostic applications.

Chung Young Hun YH Cai Hui H Steinmetz Nicole F NF

Advanced drug delivery reviews 20200627

Viral nanoparticles (VNPs) encompass a diverse array of naturally occurring nanomaterials derived from plant viruses, bacteriophages, and mammalian viruses. The application and development of VNPs and their genome-free versions, the virus-like particles (VLPs), for nanomedicine is a rapidly growing. VLPs can encapsulate a wide range of active ingredients as well as be genetically or chemically conjugated to targeting ligands to achieve tissue specificity. VLPs are manufactured through scalable f ...[more]

PMID: 32603813

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Project description:Nanoparticles (NPs) offer diagnostic and therapeutic capabilities not available with small molecules or microscale tools. As the field of molecular imaging has emerged from the blending of molecular biology with medical imaging, NP imaging is increasingly common for both therapeutic and diagnostic applications. The term theranostic describes technology with concurrent and complementary diagnostic and therapeutic capabilities. Although NPs have been FDA-approved for clinical use as transport vehicles for nearly 15 years, full translation of their theranostic potential is incomplete. However, NPs have shown remarkable success in the areas of drug delivery and magnetic resonance imaging. Emerging applications include image-guided resection, optical/photoacoustic imaging in vivo, contrast-enhanced ultrasound, and thermoablative therapy. Diagnosis with NPs in molecular imaging involves the correlation of the signal with a phenotype. The location and intensity of NP signals emanating from a living subject indicate the disease area's size, stage, and biochemical signature. Therapy with NPs uses the image for resection or delivery of a small molecule or RNA therapeutic. Ablation of the affected area is also possible via heat or radioactivity. The ideal theranostic NP includes several features: (1) it selectively and rapidly accumulates in diseased tissue; (2) it reports biochemical and morphological characteristics of the area; (3) it delivers an effective therapeutic; and (4) it is safe and biodegrades with nontoxic byproducts. Such a system contains a central imaging core surrounded by small molecule therapeutics. The system targets via ligands such as IgG and is protected from immune scavengers by a cloak of protective polymer. Although no NP has achieved all of the above criteria, many NPs possess one or more of these features. While the most clinically translatable NPs have been used in the field of magnetic resonance imaging, other types in development are quickly becoming more biocompatible through methods that modify their toxicity and biodistribution profiles. In this Account, we describe diagnostic imaging and therapeutic uses of NPs. We propose and offer examples of five primary types of nanoparticles with concurrent diagnostic and therapeutic uses.

Project description:The synthesis of self-assembled peptide nanoparticles using a facile one-pot synthesis approach is gaining increasing attention, allowing therapy in combination with diagnosis. Their drawback is limited diagnostic potential, which can be improved after necessary modifications and efficacious functionalization. Herein, a cyclic heptapeptide having the Arg-Gly-Asp-Lys-Leu-Ala-Lys sequence was modified by conjugation of the ε-amino group of the terminal lysine residue with diethylenetriamine pentaacetic acid (DTPA) as a bifunctional chelating agent (BFC) for radiolabeling with a γ-emitting radionuclide (99mTc, half-life 6.01 h; energy 140 keV). Further, the free amino group of the middle lysine residue was successfully conjugated with near-infrared fluorescence (NIRF) dye Cyanine5.5 N-succinimidyl ester (Ex/Em = 670/701 nm) by a co-assembly method to form newly designed novel NIRF dye conjugated self-assembled peptide-DTPA (Cy5.5@SAPD) nanoparticles. The fluorescent nanoparticle formation was confirmed by using a fluorescence spectrophotometer (Ex/Em = 650/701 nm), and the transmission electron microscope (TEM) images showed a size of ∼ 40 nm with a lattice fringe distance of 0.294 nm. Cytotoxicity and confocal laser scanning microscopy (CLSM) studies showed that these nanoparticles possess a high affinity for the αvβ3-integrin receptor overexpressed on brain tumor glioblastoma with an EC50 = 20 μM. Moreover, these nanoparticles were observed to have potential to internalize into U87MG cells more prominently than HEK-293 cancer cells and induce apoptosis. The apoptosis assay showed 79.5% apoptotic cells after 24 h treatment of Cy5.5@SAPD nanoparticles. Additionally, these nanoparticles were also radiolabeled with 99mTc for the single photon emission computed tomography (SPECT) imaging study in tumor-bearing female Balb/c mice. The excellent imaging feature of Cy5.5@SAPD-99mTc nanoparticles as a multimodal (SPECT/NIRF) diagnostic probe, as well as noteworthy therapeutic potential was observed. The results suggested that our newly designed novel dual-targeting dual-imaging nanoparticles may serve as an admirable theranostic probe to treat brain tumor glioblastoma multiforme.

Dataset Information

Viral nanoparticles for drug delivery, imaging, immunotherapy, and theranostic applications.

Publications

Viral nanoparticles for drug delivery, imaging, immunotherapy, and theranostic applications.

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