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Synthesis and Characterization of a "Clickable" PBR28 TSPO-Selective Ligand Derivative Suitable for the Functionalization of Biodegradable Polymer Nanoparticles.

ABSTRACT: Reactive microgliosis is a pathological hallmark that accompanies neuronal demise in many neurodegenerative diseases, ranging from acute brain/spinal cord injuries to chronic diseases, such as amyotrophic lateral sclerosis (ALS), Alzheimer's disease (AD) and age-related dementia. One strategy to assess and monitor microgliosis is to use positron emission tomography (PET) by exploiting radioligands selective for the 18 kDa translocator protein (TSPO) which is highly upregulated in the brain in pathological conditions. Several TSPO ligands have been developed and validated, so far. Among these, PBR28 has been widely adopted for PET imaging at both preclinical and clinical levels, thanks to its high brain penetration and high selectivity. For this reason, PBR28 represents a good candidate for functionalization strategies, where this ligand could be exploited to drive selective targeting of TSPO-expressing cells. Since the PBR28 structure lacks functional moieties that could be exploited for derivatization, in this work we explored a synthetic pathway for the synthesis of a PBR28 derivative carrying an alkyne group (PBR-alkyne), enabling the fast conjugation of the ligand through azide-alkyne cycloaddition, also known as click-chemistry. As a proof of concept, we demonstrated in silico that the derivatized PBR28 ligand maintains the capability to fit into the TSPO binding pocked, and we successfully exploited PBR-alkyne to decorate zwitterionic biodegradable polymer nanoparticles (NPs) resulting in efficient internalization in cultured microglia-like cell lines.

SUBMITTER: Auriemma R

PROVIDER: S-EPMC8308144 | biostudies-literature |

REPOSITORIES: biostudies-literature

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"Clickable" polymer nanoparticles: a modular scaffold for surface functionalization.

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Influence of TSPO genotype on 11C-PBR28 standardized uptake values.

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High-affinity mutant Interleukin-13 targeted CAR T cells enhance delivery of clickable biodegradable fluorescent nanoparticles to glioblastoma.

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Tailored Composite Polymer-Metal Nanoparticles by Miniemulsion Polymerization and Thiol-ene Functionalization.

Project description:A simple and modular synthetic approach, based on miniemulsion polymerization, has been developed for the fabrication of composite polymer-metal nanoparticle materials. The procedure produces well-defined composite structures consisting of gold, silver or MnFe(2)O(4) nanoparticles (∼10 nm in diameter) encapsulated within larger spherical nanoparticles of poly(divinylbenzene) (∼100 nm in diameter). This methodology readily permits the incorporation of multiple metal domains into a single polymeric particle, while still preserving the useful optical and magnetic properties of the metal nanoparticles. The morphology of the composite particles is retained upon increasing the inorganic content, and also upon redispersion in organic solvents. Finally, the ability to tailor the surface chemistry of the composite nanoparticles and incorporate steric stabilizing groups using simple thiol-ene chemistry is demonstrated.

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Orthogonally "Clickable" Biodegradable Nanofibers: Tailoring Biomaterials for Specific Protein Immobilization.

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Intravaginal gene silencing using biodegradable polymer nanoparticles densely loaded with small-interfering RNA.

| S-EPMC2693358 | biostudies-literature

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