Light-Assisted “Nano-Neutrophils” with High Drug Loading for Targeted Cancer Therapy

BACKGROUND: Nanomedicine presents a promising alternative for cancer treatment owing to its outstanding features. However, the therapeutic outcome is still severely compromised by low tumor targeting, loading efficiency, and non-specific drug release. METHODS: Light-assisted “nano-neutrophils (NMPC-NPs)”, featuring high drug loading, self-amplified tumor targeting, and light-triggered specific drug release, were developed. NMPC-NPs were composed of neutrophil membrane-camouflaged PLGA nanoparticles (NPs) loaded with a hypoxia-responsive, quinone-modified PTX dimeric prodrug (hQ-PTX(2)) and photosensitizer (Ce6). RESULTS: hQ-PTX(2) significantly enhanced the drug loading of NPs by preventing intermolecular π–π interactions, and neutrophil membrane coating imparted the biological characteristics of neutrophils to NMPC-NPs, thus improving the stability and inflammation-targeting ability of NMPC-NPs. Under light irradiation, extensive NMPC-NPs were recruited to tumor sites based on photodynamic therapy (PDT)-amplified intratumoral inflammatory signals for targeted drug delivery to inflammatory tumors. Besides, PDT could effectively eliminate tumor cells via reactive oxygen species (ROS) generation, while the PDT-aggravated hypoxic environment accelerated hQ-PTX(2) degradation to realize the specific release of PTX, thus synergistically combining chemotherapy and PDT to suppress tumor growth and metastasis with minimal adverse effects. CONCLUSION: This nanoplatform provides a prospective and effective avenue toward enhanced tumor-targeted delivery and synergistic cancer therapy.