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Glycan-targeted virus-like nanoparticles for photodynamic therapy.

ABSTRACT: Virus-like particles (VLPs) have proven to be versatile platforms for chemical and genetic functionalization for a variety of purposes in biomedicine, catalysis, and materials science. We describe here the simultaneous modification of the bacteriophage Q? VLP with a metalloporphyrin derivative for photodynamic therapy and a glycan ligand for specific targeting of cells bearing the CD22 receptor. This application benefits from the presence of the targeting function and the delivery of a high local concentration of singlet oxygen-generating payload.

SUBMITTER: Rhee JK

PROVIDER: S-EPMC3432587 | biostudies-literature | 2012 Aug

REPOSITORIES: biostudies-literature

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Glycan-targeted virus-like nanoparticles for photodynamic therapy.

Rhee Jin-Kyu JK Baksh Michael M Nycholat Corwin C Paulson James C JC Kitagishi Hiroaki H Finn M G MG

Biomacromolecules 20120724 8

Virus-like particles (VLPs) have proven to be versatile platforms for chemical and genetic functionalization for a variety of purposes in biomedicine, catalysis, and materials science. We describe here the simultaneous modification of the bacteriophage Qβ VLP with a metalloporphyrin derivative for photodynamic therapy and a glycan ligand for specific targeting of cells bearing the CD22 receptor. This application benefits from the presence of the targeting function and the delivery of a high loca ...[more]

PMID: 22827531

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Project description:Tuberculosis (TB) is an infectious disease caused by Mycobacterium tuberculosis (Mtb) that poses a serious global public health threat. Due to the high incidence of adverse reactions associated with conventional treatment regimens, there is an urgent need for better alternative therapies. CpG oligodeoxynucleotides (CpG ODNs) are synthetic oligodeoxyribonucleotide sequences. They can induce a Th1-type immune response by stimulating Toll-like receptors (TLRs) in mammalian immune cells, thus killing Mtb. However, due to the negative charge and easy degradation of CpG ODNs, it is necessary to deliver them into cells using nanomaterials. PCN-224 (hereinafter referred to as PCN), as a metal-organic framework based on zirconium ions and porphyrin ligands, not only has the advantage of high drug loading capacity, but also the porphyrin molecule in it is a type of photosensitizer, which allows these nanocomposites to play a role in photodynamic therapy (PDT) while delivering CpG ODNs. In addition, since Mtb mainly exists in macrophages, targeting anti-TB agents to macrophages is helpful to improve the anti-TB effect. Phosphatidylserine (PS) is a biological membrane phospholipid that is normally found on the inner side of cell membranes in, for example, plant and mammalian cells. When apoptosis occurs, PS can flip from the inner side of the cell membrane to the surface of the cell membrane, displaying a specific "eat-me" signal that can be recognized by specific receptors on macrophages. Therefore, we can use this macrophage-targeting property of PS to construct bio-inspired targeted drug delivery systems. In this study, we constructed PCN-CpG@PS nanocomposites. PCN-CpG@PS, combining PDT and immunotherapy, is designed to target macrophages at the site of a lesion and kill latent Mtb. We physically characterized the nanocomposites and validated their bactericidal ability in vitro and their ability to stimulate the immune system in vivo. The results demonstrated that the targeted nanocomposites have certain in vitro antituberculosis efficacy with good safety.

Dataset Information

Glycan-targeted virus-like nanoparticles for photodynamic therapy.

Publications

Glycan-targeted virus-like nanoparticles for photodynamic therapy.

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