RGD Peptide and PAD4 Inhibitor-Loaded Gold Nanorods for Chemo-Photothermal Combined Therapy to Inhibit Tumor Growth, Prevent Lung Metastasis and Improve Biosafety

Abstract

Yu Lu,1,2 Zidong Peng,1,2 Di Zhu,1,2 Yijiang Jia,1,2 Ayijiang Taledaohan,1,2 Yuanming Li,3 Jiawang Liu,4 Yanming Wang,5 Yuji Wang1,2 1Department of Medicinal Chemistry, College of Pharmaceutical Sciences of Capital Medical University, Beijing, 100069, People’s Republic of China; 2Beijing Area Major Laboratory of Peptide and Small Molecular Drugs, Engineering Research Center of Endogenous Prophylactic of Ministry of Education of China, Beijing Laboratory of Biomedical Materials, Beijing Laboratory of Oral Health, Beijing, 100069, People’s Republic of China; 3Invasive Tumor Therapies Center, Beijing Hospital, National Center of Gerontology, Beijing, 100730, People’s Republic of China; 4Medicinal Chemistry Core, The University of Tennessee Health Science Center, 579 College of Pharmacy Building, Memphis, TN, 38163, USA; 5School of Life Sciences, Henan University, Kaifeng, 475004, People’s Republic of ChinaCorrespondence: Yuji Wang 10 Xi Tou Tiao, You An Men, Beijing, 100069, People’s Republic of ChinaTel [phone]Fax [phone]Email [email protected]: A targeted drug delivery system that combines protein-arginine deiminase type-4 (PAD4) inhibitors YW3-56 (356) with PTT of NPs is constructed to both decrease the accumulation of gold in metabolic organs and reduce the dose of chemotherapeutic agents.Patients and Methods: In vitro cytotoxicity test and in vivo S180 tumor-bearing mice model were used to compare antitumor activity of 356-modified gold nanospheres and nanorods. The A549 tumor-bearing mice model was also exploited in antitumor assessment. In addition, ICP-MS, blood cell analyzer and blood biochemistry analyzer are applied for assessing the biosafety of NPs.Results: Both 356-modified gold nanospheres and nanorods showed antitumor activity. However, 356-loaded gold nanorods are found to have better tumor inhibitory activity than 356-loaded gold nanospheres in the presence of laser and without laser irradiation. Thus, 356-loaded gold nanorods are selected to be applied for chemo-photothermal combined therapy on in vivo. We find that combination therapy could inhibit tumor growth and reduce lung tumor metastasis and inflammatory infiltration compared with individual therapy. It triggers apoptosis in tumor tissue observed by TUNEL assay and TEM pictures.Conclusion: Thus, an RGD targeting and PAD4 inhibitor-loaded system are established based on chemo-photothermal combined therapy. It could inhibit tumor growth, prevent lung metastasis and improve biosafety.Keywords: gold nanospheres, gold nanorods, PAD4 inhibitor, chemo-photothermal combined therapy, biosafety

Keywords

• gold nanospheres
• gold nanorods
• pad4 inhibitor
• chemo-photothermal combined therapy
• biosafety