HPMA Copolymers: A Versatile Platform for Targeted Peptide Drug Delivery

Peptide drugs have been broadly applied in cancer treatment and diagnosis due to their ability to accurately identify biomarkers with good biocompatibility. However, their clinical application is limited by protease degradation, which induces short circulation half-life, low bioavailability, and high renal clearance. In recent years, delivery systems based on nanomaterial technology have become an important strategy to break through the bottleneck of peptide drug delivery. Among them, N-(2-hydroxypropyl) methacrylamide (HPMA) copolymers have attracted much attention due to their good biocompatibility, hydrophilicity, and low immunogenicity. The high molecular weight of HPMA copolymer-peptide can circumvent renal clearance, significantly prolong the circulation time in the body, and achieve drug accumulation and microenvironment-triggered release synergistically with EPR effects and active targeting. This review introduces the basic properties of HPMA copolymers, including solubility, biocompatibility, and tunable chemical structure. The important applications of HPMA copolymer-peptide in tumor diagnosis and treatment are discussed. This review deepens our understanding of the future development of HPMA copolymers and will provide more references for improving peptides by simple copolymers.