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Covalent assembly of nanoparticles as a peptidase-degradable platform for molecular MRI.

ABSTRACT: Ligand-conjugated microparticles of iron oxide (MPIO) have the potential to provide high sensitivity contrast for molecular magnetic resonance imaging (MRI). However, the accumulation and persistence of non-biodegradable micron-sized particles in liver and spleen precludes their clinical use and limits the translational potential of MPIO-based contrast agents. Here we show that ligand-targeted MPIO derived from multiple iron oxide nanoparticles may be coupled covalently through peptide linkers that are designed to be cleaved by intracellular macrophage proteases. The synthesized particles possess potential characteristics for targeted MRI contrast agents, including high relaxivity, unappreciable sedimentation, clearance from circulation and no overt toxicity. Importantly, we demonstrate that these particles are rapidly degraded both in vitro and in vivo, and that the targeted probes can be used for detection of inflammation in vivo using MRI. This approach provides a platform for molecular MRI contrast agents that is potentially more suitable for translation to humans.

SUBMITTER: Perez-Balderas F

PROVIDER: S-EPMC5316865 | biostudies-literature | 2017 Feb

REPOSITORIES: biostudies-literature

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Covalent assembly of nanoparticles as a peptidase-degradable platform for molecular MRI.

Perez-Balderas Francisco F van Kasteren Sander I SI Aljabali Alaa A A AA Wals Kim K Serres Sébastien S Jefferson Andrew A Sarmiento Soto Manuel M Khrapitchev Alexandre A AA Larkin James R JR Bristow Claire C Lee Seung Seo SS Bort Guillaume G De Simone Filippo F Campbell Sandra J SJ Choudhury Robin P RP Anthony Daniel C DC Sibson Nicola R NR Davis Benjamin G BG

Nature communications 20170215

Ligand-conjugated microparticles of iron oxide (MPIO) have the potential to provide high sensitivity contrast for molecular magnetic resonance imaging (MRI). However, the accumulation and persistence of non-biodegradable micron-sized particles in liver and spleen precludes their clinical use and limits the translational potential of MPIO-based contrast agents. Here we show that ligand-targeted MPIO derived from multiple iron oxide nanoparticles may be coupled covalently through peptide linkers t ...[more]

PMID: 28198362

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Project description:The future of materials chemistry will be defined by our ability to precisely arrange components that have considerably larger dimensions and more complex compositions than conventional molecular or macromolecular building blocks. However, exerting structural and constitutional control in the assembly of nanoscale entities presents a considerable challenge. Dynamic covalent nanoparticles are emerging as an attractive category of reaction-enabled solution-processable nanosized building block through which the rational principles of molecular synthetic chemistry can be extended into the nanoscale. From a mixture of two hydrazone-based dynamic covalent nanoparticles with complementary reactivity, specific molecular instructions trigger selective assembly of intimately mixed heteromaterial (Au-Pd) aggregates or materials highly enriched in either one of the two core materials. In much the same way as complementary reactivity is exploited in synthetic molecular chemistry, chemospecific nanoparticle-bound reactions dictate building block connectivity; meanwhile, kinetic regioselectivity on the nanoscale regulates the detailed composition of the materials produced. Selectivity, and hence aggregate composition, is sensitive to several system parameters. By characterizing the nanoparticle-bound reactions in isolation, kinetic models of the multiscale assembly network can be constructed. Despite ignoring heterogeneous physical processes such as aggregation and precipitation, these simple kinetic models successfully link the underlying molecular events with the nanoscale assembly outcome, guiding rational optimization to maximize selectivity for each of the three assembly pathways. With such predictive construction strategies, we can anticipate that reaction-enabled nanoparticles can become fully incorporated in the lexicon of synthetic chemistry, ultimately establishing a synthetic science that manipulates molecular and nanoscale components with equal proficiency.

Dataset Information

Covalent assembly of nanoparticles as a peptidase-degradable platform for molecular MRI.

Publications

Covalent assembly of nanoparticles as a peptidase-degradable platform for molecular MRI.

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