Poly(ethylene glycol) alternatives in biomedical applications

Poly(ethylene glycol) (PEG) as gold standard has been extensively conjugated to diagnostic and therapeutic agents or decorated on the surface of nanoplatforms, which is known as PEGylation. After the PEGylation, these formations are expected to achieve superior diagnostic and therapeutic effects. However, in-depth studies indicate that PEG abuse can also cause severe side effects, such as the production of anti-PEG antibodies, hypersensitivity reactions and accelerated blood clearance (ABC) phenomenon, which may generate toxic species and greatly compromise their therapeutic efficacy. In this review, after the introduction of PEG's pros and cons, categories and characteristics of PEG alternatives including poly(N-vinylpyrrolidone), polyacrylamides, polybetaines, poly(2-oxazoline)s, polyesters and polysarcosine are presented, followed by discussion about the synthesis and characterization of these PEG alternatives. Afterwards, updated biomedical applications of these PEG alternatives are illustrated from the following subsections, i.e., PEG alternative-agent conjugates, PEG alternative-tethered nanocarriers for imaging and drug delivery, PEG alternative-modified hydrogels and PEG alternatives for antifouling surface coating. In the end, conclusions and future perspectives of PEG alternatives are given. It is envisioned that these PEG alternatives can bring a great opportunity to construct efficient nanoplatforms for precise nanomedicine.