Pathogen‐Mimicking MnO Nanoparticles for Selective Activation of the TLR9 Pathway and Imaging of Cancer Cells

Abstract

Here, design of the first pathogen‐mimicking metal oxide nanoparticles with the ability to enter cancer cells and to selectively target and activate the TLR9 pathway, and with optical and MR imaging capabilities, is reported. The immobilization of ssDNA (CpG ODN 2006) on MnO nanoparticles is performed via the phosphoramidite route using a multifunctional polymer. The multifunctional polymer used for the nanoparticle surface modification not only affords a protective organic biocompatible shell but also provides an efficient and convenient means for loading immunostimulatory oligonucleotides. Since fluorescent molecules are amenable to photodetection, a chromophore (Rhodamine) is introduced into the polymer chain to trace the nanoparticles in Caki‐1 (human kidney cancer) cells. The ssDNA coupled nanoparticles are used to target Toll‐like receptors 9 (TLR9) receptors inside the cells and to activate the classical TLR cascade. The presence of TLR9 is demonstrated independently in the Caki‐1 cell line by western blotting and immunostaining techniques. The magnetic properties of the MnO core make functionalized MnO nanoparticles potential diagnostic agents for magnetic resonance imaging (MRI) thereby enabling multimodal detection by a combination of MR and optical imaging methods. The trimodal nanoparticles allow the imaging of cellular trafficking by different means and simultaneously are an effective drug carrier system.

Activated Ester Containing Polymers: Opportunities and Challenges for the Design of Functional Macromolecules

“…501 Similarly, DNAcoated MnO nanoparticles have been prepared and utilized as specific cellular cargos. 502,503 Those selected examples nicely document the versatility of preparing highly specific and multifunctional polymers by a simple series of aminolysis steps using an activated ester precursor polymer.…”

Water-Soluble and Biocompatible MnO@PVP Nanoparticles for MR Imaging <I>In Vitro</I> and <I>In Vivo</I>

“…MRI has further advanced by the development of contrast agents that enable more specific and clearer images and enlargements of detectable organs and systems, 15 leading to a wide scope of applications of MRI not only for diagnostic radiology but also for therapeutic medicine. In particular, magnetic nanocrystals have capabilities as excellent magnetic resonance signal enhancers [16][17][18][19] that can resolve the weakness of modern MRI technique. The current MRI contrast agents are in the form of T 1 -positive agents of paramagnetic species 20 and T 2 -negative agents of superparamagnetic particles.…”

A mussel-inspired chitooligosaccharide based multidentate ligand for highly stabilized nanoparticles

“…To ensure the stability of IONPs and to promote their dispersion in aqueous media, there are two common coating strategies to convert hydrophobic ones into hydrophilic and functional nanoparticles. [25][26][27][28][29][30] More importantly, for the biofunctionalization of the nanoparticles, a binding site can be provided for other bioactive molecules that can further extend the biomedical applications. [10][11][12][13][14][15] The second approach is to encapsulate the nanoparticles with amphiphilic polymers in a micelle format.…”