Stealth nanoparticles in oncology: Facing the PEG dilemma

Nanoparticles (Nps) have revolutionized the landscape of many treatments, by modifying not only pharmaco-kinetic properties of the encapsulated agent, but also providing a significant protection of the drug from non -desired interactions, and reducing side-effects of the enclosed therapeutic, enabling co-encapsulation of possibly synergistic compounds or activities, allowing a controlled release of content and improving the thera-peutic effect.Nevertheless, in systemic circulation, Nps suffer a rapid removal by opsonisation and the action of Mono-nuclear phagocyte system (MPS). To overcome this problem, different polymers, in particular Polyethyleneglycol (PEG), have been used to cover the surface of these nanocarriers forming a hydrophilic layer that allows the delay of the removal.These advantages contrast with some drawbacks such as the difficulty to interact with cell membranes and the development of immunological reactions, conforming the known, PEG dilemma. To address and minimize this phenomenon, different strategies have been applied.Therefore, this review aims to summarize the state of the art of Pegylation strategies, comment in depth on the principal characteristics of PEG and describe the main alternatives, which are the use of cleavable PEG, addition of different polymers or even use other derivatives of cell membranes to camouflage Nps.

Automated summary

Nanoparticles (Nps) have revolutionized treatments by modifying drug properties and providing protection, but they are easily removed in circulation. Polyethyleneglycol (PEG) and other polymers have been used to delay removal. However, this covering also has drawbacks, requiring alternative strategies to address the issue.