Nanoparticle PEGylation for imaging and therapy

Abstract

Nanoparticles are an essential component in the emerging field of nanomedical imaging and therapy. When deployed in vivo, these materials are typically protected from the immune system by polyethylene glycol (PEG). A wide variety of strategies to coat and characterize nanoparticles with PEG has established important trends on PEG size, shape, density, loading level, molecular weight, charge and purification. Strategies to incorporate targeting ligands are also prevalent. This article presents a background to investigators new to stealth nanoparticles, and suggests some key considerations needed prior to designing a nanoparticle PEGylation protocol and characterizing the performance features of the product.

Figure 1. Nanoparticle applications of polyethylene glycol

(A) The use of NPs in imaging involves different modalities, including optical and radionuclide techniques. In therapy, diverse NPs carry a range of payloads, including radiotherapy, nucleic acids and small molecules. (B) PEGylated NP, indicating a firmer metallic or polymeric core (yellow) with a surrounding cloud of flexible PEG chains (red). (C) Monomers of ethylene glycol are polymerized into PEG for NP coating. PEG contains the linkage group (R₁) and a terminus that interacts with solvent (R₂). NP: Nanoparticle; PEG: Polyethylene glycol.

Figure 2. Polyethylene glycol prevents uptake by the reticuloendothelial system

(A) Nanoparticles (A1) are coated with opsonin proteins (A2) and associate with macrophages (A3) for transit to the liver (A4). Macrophages stationary in the liver, known as Kupffer cells, also participate in nanoparticle scavenging. (B) Nanoparticles coated with PEG coating (B1) prevents this opsonization (B2), resulting in decreased liver accumulation (B3) and increased availability of the NP for imaging or therapy. NP: Nanoparticle; PEG: Polyethylene glycol.

Figure 3. Polyethylene glycol background

(A) The number of literature citations for `nanoparticle + PEG' as determined by Chemical Abstract Services indicates a progressive increase in the last decade. (B) The Flory radius of the PEG coil increases as a function of the number of monomers (n); see Equation 1. PEG: Polyethylene glycol.

Figure 4. Gold spherical nanoparticle with two types of polyethylene glycol modifications

Polyethylene glycol orientations on the nanoparticle surface include (A) low-density mushroom configurations and (B) high-density brush-type arrangements.

Figure 5. Increased affinity for targeted nanoparticles

(A) In targeted nanoparticles, the ligand (blue) may either be localized on the distal end of the polyethylene glycol chain or (B) at the nanoparticle surface. A wide variety of ligand and nanoparticle combinations have been reported, including the examples in this article. See Table 4.