International Journal of Nanomedicine (Jun 2023)
Multi-Site Attack, Neutrophil Membrane-Camouflaged Nanomedicine with High Drug Loading for Enhanced Cancer Therapy and Metastasis Inhibition
Abstract
Ran Huang,1,* Daopeng Fan,1,* Hanghang Cheng,1 Jian Huo,1 Shuqi Wang,1 Hua He,1 Gaiping Zhang1,2 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*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] Gaiping Zhang, 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]: Advanced breast cancer is a highly metastatic tumor with high mortality. Simultaneous elimination of primary tumor and inhibition of neutrophil-circulation tumor cells (CTCs) cluster formation are urgent issues for cancer therapy. Unfortunately, the drug delivery efficiency to tumors and anti-metastasis efficacy of nanomedicine are far from satisfactory.Methods: To address these problems, we designed a multi-site attack, neutrophil membrane-camouflaged nanoplatform encapsulating hypoxia-responsive dimeric prodrug hQ-MMAE2 (hQNM-PLGA) for enhanced cancer and anti-metastasis therapy.Results: Encouraged by the natural tendency of neutrophils to inflammatory tumor sites, hQNM-PLGA nanoparticles (NPs) could target delivery of drug to tumor, and the acute hypoxic environment of advanced 4T1 breast tumor promoted hQ-MMAE2 degradation to release MMAE, thus eliminating the primary tumor cells to achieve remarkable anticancer efficacy. Alternatively, NM-PLGA NPs inherited the similar adhesion proteins of neutrophils so that NPs could compete with neutrophils to interrupt the formation of neutrophil-CTC clusters, leading to a reduction in extravasation of CTCs and inhibition of tumor metastasis. The in vivo results further revealed that hQNM-PLGA NPs possessed a perfect safety and ability to inhibit tumor growth and spontaneous lung metastasis.Conclusion: This study demonstrates the multi-site attack strategy provides a prospective avenue with the potential to improve anticancer and anti-metastasis therapeutic efficacy.Keywords: neutrophil membrane, high drug loading, hypoxia-responsive, CTC-neutrophil cluster, cancer and anti-metastasis therapy
