Albumin‐Mediated Delivery of Bioactive Peptides for Pancreatic Cancer Therapy

Bioactive peptides are promising agents for therapeutic applications; however, their small size leads to poor stability, low bioavailability, and rapid renal clearance, so the widespread use is limited. To address these issues, fusing or conjugating peptides to suitable molecular scaffolds is required. Here, human serum albumin (HSA) is used as a delivery carrier for human β‐defensin‐2 peptide (HBD2) in production of HSA‐delivered defensin complex (ADDC) to facilitate its cellular uptake and transport to intracellular targets. Fusion or conjugation can improve the stability of HBD2, as well as extend its circulation time and promote its accumulation in tumors, thereby enhancing the therapeutic efficacy. Herein, ADDC functions as a protective structure against the harsh external environment and serves as a passive tumor‐targeting agent. The data show that the combination of ADDC with clinically relevant drugs, such as Doxorubicin, Gemcitabine, Cisplatin, and Cetuximab, significantly increases the cytotoxicity of ADDC toward human pancreatic cancer cells. Bioinformatics analysis also reveals that ADDC may affect the metabolic processes, gene transcription, and apoptosis of pancreatic cancer cells. Collectively, ADDC exhibits tumor‐specific targeting capability, low systemic toxicity, and enhanced antitumor efficacy in a mouse model of pancreatic cancer.