Linming Li,1,* Yan Chen,1,* Qingpeng Wang,1 Zuojie Li,1 Zhifang Liu,1 Xuewen Hua,1 Jun Han,1 Chunxiao Chang,2 Zhengping Wang,1,3 Dacheng Li1,4 1Institute of Biopharmaceutical Research, Liaocheng University, Liaocheng, 252059, People’s Republic of China; 2Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, 250022, People’s Republic of China; 3Liaocheng High-Tech Biotechnology Co., Ltd, Liaocheng, 252059, People’s Republic of China; 4Shandong Provincial Key Laboratory of Chemical Energy Storage and Novel Cell Technology, Liaocheng University, Liaocheng, 252059, People’s Republic of China*These authors contributed equally to this workCorrespondence: Qingpeng WangInstitute of Biopharmaceutical Research, Liaocheng University, Liaocheng, 252059, People’s Republic of ChinaTel/Fax +86 635 8239773Email lywqp@126.comChunxiao ChangShandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, 250022, People’s Republic of ChinaEmail changcx-111@163.comBackground: Platinum(IV) complexes with inflammation inhibitory properties are much favored in improving antitumor activities. Nanodrug-delivery system as a preferable measure for antitumor therapy are widely explored in platinum(IV) drug delivery.Purpose: The aim for this study was to develop novel bovine serum albumin (BSA) nanoparticles (NPs) based on naproxen platinum(IV) complexes to display a synergistic antitumor mechanism targeting cyclooxygenase-2 (COX-2), metalloproteinase-9 (MMP-9) and inducible nitric oxide synthase (iNOS).Methods: Herein, we reported the preparation of two BSA NPs of naproxen platinum(IV) complexes, and their antitumor activities were investigated in vitro and in vivo.Results: Both NPs possessed relatively uniform size and good stability for 30 days in aqueous solution. They exhibited prominent antitumor activities in vitro, and showed great potential in reversing drug resistance. Furthermore, these two NPs played superior tumor growth suppression in vivo in contrast to the free compounds, which were comparable to that of cisplatin and oxaliplatin, but induced lower toxic influences than platinum(II) drugs especially to spleen and liver. Moreover, the naproxen platinum(IV) NPs could decrease tumor inflammation targeting COX-2, MMP-9 and iNOs, and decreasing NO production, which would be in favor of enhancing the antitumor competence, and reducing toxicity.Conclusion: Taken together, BSA NPs of naproxen platinum(IV) complexes demonstrated a powerful antitumor efficacy in vitro and in vivo. The platinum(IV) NPs with inflammation inhibitory competence targeting multiple enzymes reported in this work afford a new strategy for the development of antitumor therapy to overcome drawbacks of clinical platinum(II) drugs.Keywords: bovine serum albumin nanoparticles, cyclooxygenase-2, metalloproteinases-9, inducible nitric oxide synthase, synergistic antitumor efficacy
