Drug-Polymer Hybrid Macromolecular Engineering: Degradable PEG Integrated by Platinum(IV) for Cancer Therapy

Drug delivery systems (DDSs) based on macromolecular engineering have attracted much attention in biotechnology and medicine due to their versatile and tunable chemistry. However, concern about the biosafety issue of polymeric carriers is increasing. For example, non-biodegradability of high-molecular-weight poly(ethylene glycol) (PEG) causes serious side effects. To solve this, here we propose a safer, simpler, and more efficient polymeric DDS with a drug-polymer hybrid macromolecular engineering concept. The DDS consists of a degradable PEG integrated with a hydrophobic platinum(IV) prodrug with responsive bonds in the polymeric backbone. This polymer maintains the advantages of both high-molecular-weight PEG in improving the pharmacokinetics of drugs with high drug accumulation in tumor tissues and low-molecular-weight PEG, which is easily excreted, reducing its side effects. It is also associated with tunable amphiphilicity and drug loading efficiency, contributed by the drug-polymer hybrid. This work provides a novel strategy for the design of polymeric biodegradable DDSs.