Effective Triple-Negative Breast Cancer Targeted Treatment Using iRGD-Modified RBC Membrane-Camouflaged Nanoparticles

Jingbin Huang,* Wenjing Lai,* Qing Wang, Qin Tang, Changpeng Hu, Min Zhou, Fengling Wang, Dandan Xie, Qian Zhang, Wuyi Liu, Zhe Zhang, Rong Zhang Department of Pharmacy, The Second Affiliated Hospital of Army Medical University, ChongQing, People’s Republic of China*These authors contributed equally to this workCorrespondence: Rong Zhang; Zhe Zhang Email xqpharmacylab@126.com; 15086988023@163.comIntroduction: Triple-negative breast cancer (TNBC) has the high degree of malignancy and aggressiveness. There is no targeted therapy drug. Many studies have shown that RBC membrane-coated nanoparticles achieve biological camouflage. In addition, the RGD module in the iRGD mediates the penetration of the vector across the tumor blood vessels to the tumor tissue space. Therefore, we developed iRGD-RM-(DOX/MSNs) by preparing MSNs loaded with doxorubicin as the core, and coating the surface of the MSNs with iRGD-modified RBC membranes.Methods: iRGD-RM-(DOX/MSNs) were fabricated using physical extrusion. In addition, their physical and chemical characterization, hemolytic properties, in vivo acute toxicity and inflammatory response, in vitro and in vivo safety, and qualitative and quantitative cellular uptake by RAW 264.7 cells and MDA-MB-231 cells were evaluated and compared. Furthermore, we examined the antitumor efficacy of iRGD-RM-(DOX/MSN) nanoparticles in vitro and in vivo.Results: iRGD-RM-(DOX/MSNs) have reasonable physical and chemical properties. iRGD-RM-(DOX/MSNs) escaped the phagocytosis of immune cells and achieved efficient targeting of nanoparticles at the tumor site. The nanoparticles showed excellent antitumor effects in vivo and in vitro.Conclusion: In this study, we successfully developed biomimetic iRGD-RM-(DOX/MSNs) that could effectively target tumors and provide a promising strategy for the effective treatment of TNBC.Keywords: RBC membrane, iRGD peptide, biological camouflage, targeted treatment, Triple-negative breast cancer