Polyethylene glycol-mediated functionalization of nanodelivery systems for improving their pharmacokinetic profile and anticancer efficacy

PEGylation has emerged as a promising adaptation in the architecture of nanodelivery systems to improve their physicochemical properties, stability, circulation time, passive targeting to tumor tissues, and anticancer efficacy. Owing to its heterogeneity, metastatic and recurrence potential, and ability to develop chemoresistance, the treatment of cancer is one of the serious challenges for oncologists. The nanotechnology-mediated delivery of chemotherapeutics has revolutionized the oncotherapy through controlling their release kinetics, prolonging their plasma half-life, and enabling their passive diffusion into the tumor tissues. Despite numerous biopharmaceutical advantages, the clinical translation of nanomedicines is hampered due to their recognition and elimination from the body by the mononuclear phagocyte system (MPS). This review presents an overview on PEGylation including the principle, types of polyethylene glycol (PEG)-linkers and their attachment chemistries, current challenges, and application of PEGylation for the treatment of various types of cancer. The covalent conjugation of PEG with drug(s), biologicals, or nanomaterials or its adsorptive coating on the surface of nanomaterials has shown promising improvements in their physicochemical properties, pharmacokinetic profile, cellular internalization, tumor biodistribution, and anticancer efficacy. The current challenges to PEGylated drug(s) or nanomaterials and plausible adaptations to tackle these issues have also been thoroughly discussed in this review.