Stealth Coating of Nanoparticles in Drug-Delivery Systems - PubMed (original) (raw)

Review

Stealth Coating of Nanoparticles in Drug-Delivery Systems

See Yee Fam et al. Nanomaterials (Basel). 2020.

Abstract

Nanoparticles (NPs) have emerged as a powerful drug-delivery tool for cancer therapies to enhance the specificity of drug actions, while reducing the systemic side effects. Nonetheless, NPs interact massively with the surrounding physiological environments including plasma proteins upon administration into the bloodstream. Consequently, they are rapidly cleared from the blood circulation by the mononuclear phagocyte system (MPS) or complement system, resulting in a premature elimination that will cause the drug release at off-target sites. By grafting a stealth coating layer onto the surface of NPs, the blood circulation half-life of nanomaterials can be improved by escaping the recognition and clearance of the immune system. This review focuses on the basic concept underlying the stealth behavior of NPs by polymer coating, whereby the fundamental surface coating characteristics such as molecular weight, surface chain density as well as conformations of polymer chains are of utmost importance for efficient protection of NPs. In addition, the most commonly used stealth polymers such as poly(ethylene glycol) (PEG), poly(2-oxazoline) (POx), and poly(zwitterions) in developing long-circulating NPs for drug delivery are also thoroughly discussed. The biomimetic strategies, including the cell-membrane camouflaging technique and CD47 functionalization for the development of stealth nano-delivery systems, are highlighted in this review as well.

Keywords: drug delivery; nanoparticles; opsonization; phagocytosis; polymer; stealth.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1

Figure 1

A simplified overview of different activation pathways of the complement system. There are three complement activation pathways: the classical pathway, which is activated by antibody binding or the direct fixation of complement component C1q bound to zymogens C1r and C1s on the surface of an antigen; the lectin pathway, which is triggered by the binding of mannan-binding lectin (MBL) activated by MBL-associated serine proteases (MASP), namely MASP1 and MASP2, to mannose contained on the surface of an antigen; and the alternative pathway, which is triggered directly by the binding of spontaneously activated complement component on the surface of an antigen. The complement enzymatic cascades of each pathway generate a key protease called C3 convertase that cleaves C3 into C3b and C3a. This complement activation leads to eventual antigen opsonization, inflammatory responses, and membrane lysis.

Figure 2

Figure 2

Chemical structures of the stealth polymers. The alpha (α) and omega (ω) termini of poly(2-methyl-2-oxazoline) and poly(2-ethyl-2-oxazoline) are indicated in circles.

Figure 3

Figure 3

Schematic representations of CD47 regulation on phagocytosis of nanoparticles (NPs). (a) CD47 coated on a nanoparticle interacts with the signal regulatory protein alpha (SIRPα) expressed on the surface of the macrophage, triggering a potent “don’t-eat-me” signal, which inhibits phagocytosis; (b) A nanoparticle without CD47 functionalization is recognized by macrophage for particle engulfment and phagocytosis.

Figure 4

Figure 4

Schematic representations of poly(ethylene glycol) (PEG) conformations on NPs. (a) At low surface coverage, PEG chains are located closer to the particle’s surface, leading to a mushroom conformation; (b) At high surface coverage, PEG chains are lack of mobility and extended away from the particle’s surface, leading to a brush conformation. RF represents the Flory radius of the PEG graft; D represents the distance between the adjacent PEG grafts; L represents the thickness of the grafted PEG layer (the diagrams are drawn not to scale).

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