Novel Core–Shell Polyamine Phosphate Nanoparticles Self‐Assembled from PEGylated Poly(allylamine hydrochloride) with Low Toxicity and Increased In Vivo Circulation Time

Abstract

An approach for reducing toxicity and enhancing therapeutic potential of supramolecular polyamine phosphate nanoparticles (PANs) through PEGylation of polyamines before their assembly into nanoparticles is presented here. It is shown that the number of polyethylene glycol (PEG) chains for polyamine largely influence physico‐chemical properties of PANs and their biological endpoints. Poly(allylamine hydrochloride) (PAH) are functionalized through carbodiimide chemistry with three ratios of PEG molecules per PAH chain: 0.1, 1, and 10. PEGylated PAH is then assembled into PANs by exposing the polymer to phosphate buffer solution. PANs decrease size and surface charge with increasing PEG ratios as evidenced by dynamic light scattering and zeta potential measurements, with the ten PEG/PAH ratio PANs having practically zero charge. Small angle X‐ray scattering (SAXS) proves that PEG chains form a shell around a polyamine core, which is responsible for the screening of positive charges. MTT experiments show that the screening of amine groups decreases nanoparticle toxicity, with the lowest toxicity for the 10 PEG/PAH ratio. Fluorescence correlation spectroscopy (FCS) proves less interaction with proteins for PEGylated PANs. Positron emission tomography (PET) imaging of 18F labelled PANs shows longer circulation time in healthy mice for PEGylated PANs than non‐PEGylated ones.

Gold nanoparticles decorated with monosaccharides and sulfated ligands as potential modulators of the lysosomal enzyme N-acetylgalactosamine-6-sulfatase (GALNS)

“…30 Au electron density and β- d -galactoside-coating electron density were used to adequately fit experimental data; further details concerning this approach can be found in the literature. 31 The gold core diameter has been fitted considering its polydispersion (in agreement with TEM data, Fig. S5†), while the organic shell thickness has been considered as a monodisperse parameter.…”

Poly(allylamine)-tripolyphosphate Ionic Assemblies as Nanocarriers: Friend or Foe?

“…One approach used to reduce cell toxicity involves screening amino groups by grafting polyamines with PEG . For instance, it has been recently reported that PEGylation of PAH reduces the toxicity of PAH/phosphate nanocomplexes . The authors found that a core–shell structure is formed with the PEG chains forming the outer layer.…”

“…62 For instance, it has been recently reported that PEGylation of PAH reduces the toxicity of PAH/phosphate nanocomplexes. 63 The authors found that a core−shell structure is formed with the PEG chains forming the outer layer. This PEG shell around a polyamine core shields the positive charges of the PAHs, reducing the zeta potential from +20 mV for unmodified complexes to less than +5 mV for the nanocomplexes based on PAH-PEGylated.…”

Positron Emission Tomography Studies of the Biodistribution, Translocation, and Fate of Poly Allyl Amine‐Based Carriers for Sirna Delivery by Systemic and Intratumoral Administration

“…Functionalization with polyethylene glycol (PEG) and oleic acid has been shown to decrease polyamine toxicity. [ 21 ] NPs made of oleic acid‐modified PAH show indeed low toxicity with a transfection efficacy similar to Lipofectamine reagents. [ 22 ]…”