Advances in Peptide-Functionalized Polymeric Nanocarriers for Cancer Therapy

Background/Objectives: Peptide-functionalized polymeric nanocarriers are redefining targeted cancer therapy by combining the molecular specificity of peptides with the structural versatility of polymers. This review aims to highlight recent advances in peptide-functionalized polymeric nanocarrier systems designed to overcome key biological barriers to effective drug delivery. Methods: This review examines peptide-functionalized polymeric nanocarriers, including polymeric nanoparticles, micelles, polyplexes, and polymer–drug conjugates engineered with targeting, cell-penetrating, tumor-penetrating, and tumor microenvironment-responsive peptides. Emerging design strategies, including dual- and multi-peptide functionalization, stimuli-responsive linkers, and prodrug-like polymer architectures, are reviewed. Results: These peptide-functionalized polymeric nanocarrier systems have been investigated for the delivery of diverse therapeutic cargos, including small-molecule drugs, peptides, proteins, and nucleic acids. They demonstrate enhanced tumor localization, improved cellular internalization, and spatiotemporally controlled drug release, thereby contributing to significantly improved therapeutic efficacy and reduced systemic toxicity in preclinical studies. Advanced designs incorporating multiple peptide functionalities further enable precise modulation of drug delivery and therapeutic outcomes. Conclusions: Peptide-functionalized polymeric nanocarriers represent a versatile and powerful platform for next-generation cancer therapeutics. However, challenges related to stability, large-scale manufacturability, and clinical translation persist. Integration of data-driven approaches and artificial intelligence holds promise for accelerating optimization and facilitating clinical translation.