Design of Synthetic Polymer Nanoparticles Specifically Capturing Indole, a Small Toxic Molecule

Abstract

Synthetic polymers are of interest as stable and cost-effective biomolecule-affinity reagents, since these polymers interact with target biomolecules both in vitro and in the bloodstream. However, little has been reported about orally administered polymers capable of capturing a target molecule and inhibiting its intestinal absorption. Here, we describe the design of synthetic polymer nanoparticles (NPs) specifically capturing indole, a major factor exacerbating chronic kidney disease, in the intestine. N-isopropylacrylamide-based NPs were prepared with various hydrophobic monomers. The amounts of indole captured by NPs depended on the structures and feed ratios of the hydrophobic monomers and the polymer density but not on the particle size. The combination of hydrophobic and quadrupole interaction was effective to enhance the affinity and specificity of NPs for indole. The optimized NPs specifically inhibited intestinal absorption of orally administered indole in mice. These results showed the potential of synthetic polymer NPs for inhibiting the intestinal absorption of a target molecule.

Design of Functional Nanoparticles for Intractable Disease Therapy

“…40,41) Although IS is excreted from the kidney in healthy subjects, it accumulates in the kidneys and causes damage in patients with chronic kidney disease. 42) Thus, inhibition of indole adsorption from the intestine is one critical strategy. Because indole is a hydrophobic and aromatic compound, NPs were prepared with NIPAm, Bis and TBAm, N-phenyacrylamide (PAA), or 2,3,4,5,6-pentafluorophenyl acrylamide (5FPAA) 43) (Fig.…”

Influence of Purification Process on the Function of Synthetic Polymer Nanoparticles

“…13) Homogenous oligomers neutralize venom peptides by precise molecular recognition of critical domain. 14) Rationally designed acrylamide-based copolymers bind to small molecules, 15) peptides, 16) and proteins 17) with high selectivity by optimizing functional monomer structure and feed ratio. 18,19) It has been also reported that polymer flexibility and length are important for the induction of high target specificity and affinity.…”

“…13,25,26) Relatively low-molecular-weight polymers (e.g., dendrimers and oligomers) are usually purified by chromatography and extraction. 11,12,14) Therefore, purification method was not unified. Thus, sometimes, several methods are used even for the same materials.…”

Synthetic hydrogel nanoparticles for sepsis therapy

“…This work was motivated by prior studies that established the physiochemical properties of synthetic hydrogel nanoparticles (HNPs) could be modi ed to tune both a nity and selectivity for speci c biomacromolecule targets. Examples include a nity reagents for small molecules 21 , peptides 22,23,24 , enzymes 25 , polysaccharides 26 , lipid/lipid-like macromolecules 27 and proteins 28,29 including the angiogenesis signaling protein VEGF 165 30, 31 . The HNPs have a high capacity for target peptides compared with antibodies by sequestering them not only on their surface, but also within the HNPs themselves 23 .…”