Design of Polymeric Carriers for Intracellular Peptide Delivery in Oncology Applications

In recent decades, peptides, which can possess high potency, excellent selectivity, and low toxicity, have emerged as promising therapeutics for cancer applications. Combined with an improved understanding of tumor biology and immuno-oncology, peptides have demonstrated robust antitumor efficacy in preclinical tumor models. However, the translation of peptides with intracellular targets into clinical therapies has been severely hindered by limitations in their intrinsic structure, such as low systemic stability, rapid clearance, and poor membrane permeability, that impede intracellular delivery. In this Review, we summarize recent advances in polymer-mediated intracellular delivery of peptides for cancer therapy, including both therapeutic peptides and peptide antigens. We highlight strategies to engineer polymeric materials to increase peptide delivery efficiency, especially cytosolic delivery, which plays a crucial role in potentiating peptide-based therapies. Finally, we discuss future opportunities for peptides in cancer treatment, with an emphasis on the design of polymer nanocarriers for optimized peptide delivery.

Automated summary

Peptides as promising cancer therapeutics have shown robust antitumor efficacy, but the translation into clinical therapies is hindered by inherent limitations in their structure, hindering intracellular delivery. Strategies to engineer polymeric materials for increased peptide delivery efficiency, especially cytosolic delivery, play a crucial role in potentiating peptide-based cancer therapies. Future opportunities for peptides in cancer treatment lie in the design of polymer nanocarriers for optimized peptide delivery.