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

Abstract

Daopeng Fan,1,* Shuqi Wang,1,* Ran Huang,1,* Xiaoning Liu,1 Hua He,1 Gaiping Zhang1– 3 1College of Veterinary Medicine, International Joint Research Center of National Animal Immunology, Henan Agricultural University, Zhengzhou, 450046, People’s Republic of China; 2Longhu Laboratory, Zhengzhou, 450046, People’s Republic of China; 3School of Advanced Agriculture Sciences, Peking University, Beijing, 100871, People’s Republic of China*These authors contributed equally to this workCorrespondence: Hua He, College of Veterinary Medicine, International Joint Research Center of National Animal Immunology, Henan Agricultural University, Zhengzhou, 450046, People’s Republic of China, Email [email protected]: 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-PTX2) and photosensitizer (Ce6).Results: hQ-PTX2 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-PTX2 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.Keywords: neutrophil, self-amplified tumor targeting, high drug loading, hypoxia-responsive, chemo-photodynamic therapy

Keywords

• neutrophil
• self-amplified tumor targeting
• high drug loading
• hypoxia-responsive
• chemo-photodynamic therapy