Albumin Nanoparticles Harness Activated Neutrophils to Cross Vascular Barriers for Targeted Subcutaneous and Orthotopic Colon Cancer Therapy

Colorectal cancer (CRC) therapy faces challenges due to limited drug penetration across the blood–tumor barrier. Neutrophils, with their natural ability to migrate to inflamed and tumor sites, offer a promising cell-mediated delivery strategy. This study developed albumin nanoparticles loaded with 6-shogaol (NPs/6-shogaol) and utilized activated neutrophils as carriers to transport the nanoparticles across vascular barriers for colon cancer therapy. The physicochemical properties, biocompatibility, and targeting efficiency of the NPs were evaluated in vitro and in vivo. The formulated NPs/6-shogaol exhibited favorable physicochemical properties, including a uniform nano-scale size (~150 nm), negative zeta potential, and high drug loading efficiency. In both subcutaneous and orthotopic colon cancer models, neutrophil-mediated delivery significantly enhanced tumor accumulation of 6-shogaol, inhibited tumor growth, and induced apoptosis by suppressing neutrophil elastase (NE) expression. Notably, no significant systemic toxicity was observed. This neutrophil-hitchhiking albumin nanoplatform provides a targeted and biocompatible strategy for effective colon cancer therapy.