Dendrimer

Conjugate

Polyethylene glycol

Materials science

Smart polymer

Drug

Immunology

Drug delivery

Polymer

Combinatorial chemistry

Drug carrier

Nanotechnology

Organic chemistry

Immune system

Mathematics

Immunogenicity

Pharmacology

Mathematical analysis

Medicine

Chemistry

Nature Reviews Drug Discovery

Polymer–drug conjugates have long been a mainstay of the drug delivery field, with several conjugates successfully translated into clinical practice. The conjugation of therapeutic agents to polymeric carriers, such as polyethylene glycol, offers several advantages, including improved drug solubilization, prolonged circulation, reduced immunogenicity, controlled release and enhanced safety. In this Review, we discuss the rational design, physicochemical characteristics and recent advances in the development of different classes of polymer–drug conjugates, including polymer–protein and polymer–small-molecule drug conjugates, dendrimers, polymer nanoparticles and multifunctional systems. Current obstacles hampering the clinical translation of polymer–drug conjugate therapeutics and future prospects are also presented. The conjugation of therapeutic agents to polymer carriers, such as polyethylene glycol (PEG), can control drug delivery, enhance solubilization, increase efficacy and improve pharmacokinetics. Here, Grinstaff, Colson and Ekladious discuss recent advances in the preclinical and clinical development of different classes of polymer–drug conjugates and highlight current challenges and future directions.

Polymer–drug conjugate therapeutics: advances, insights and prospects