International Journal of Nanomedicine (Apr 2023)
Fe3+@PDOPA‑b‑PSar Nanoparticles for Magnetic Resonance Imaging and Cancer Chemotherapy
Abstract
Wei Sun,1,2,* Songyi Xu,3,* Tianlun Shen,1,3,* Guangyao Li,1 Jingfeng Zhang,2 Chunshu Pan,1,2 Wei Lu,1,2 Xiangrui Liu,1 Jianjun Zheng,2 Jun Ling,1,3 Jihong Sun1 1Department of Radiology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, People’s Republic of China; 2Department of Radiology, Ningbo No. 2 Hospital, Ningbo, People’s Republic of China; 3MOE Key Laboratory of Macromolecular Synthesis and Functionalization, Department of Polymer Science and Engineering, Zhejiang University, Hangzhou, People’s Republic of China*These authors contributed equally to this workCorrespondence: Jihong Sun, Department of Radiology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Tel +86 13857176538, Email [email protected] Jianjun Zheng, President of Ningbo No. 2 Hospital, Ningbo, People’s Republic of China, Tel +86 574 83870280, Email [email protected]: Chemotherapy treatments for cancer are always accompanied by a low concentration of drug delivered in the tumor area and severe side effects including systemic toxicity. Improving the concentration, biocompatibility, and biodegradability of regional chemotherapy drugs is a pressing challenge in the field of materials.Methods: N-Phenyloxycarbonyl-amino acids (NPCs) which exhibit significant tolerance to nucleophiles, such as water and hydroxyl-containing compounds, are promising monomers for the synthesis of polypeptides and polypeptoids. Cell line and mouse models were used to comprehensively explore how to enhance the tumor MRI signal and evaluate the therapeutic effect of Fe@POS-DOX nanoparticles.Results: In this study, poly(3,4-dihydroxy-L-phenylalanine)-b-polysarcosine (PDOPA-b-PSar, simplified as POS) was synthesized by the block copolymerization of DOPA-NPC with Sar-NPC. Fe@POS-DOX nanoparticles were prepared in order to utilize the strong chelation of catechol ligands to iron (III) cations and the hydrophobic interaction between DOX and DOPA block to deliver chemotherapeutics to tumor tissue. The Fe@POS-DOX nanoparticles exhibit high longitudinal relaxivity (r1 = 7.06 mM− 1·s− 1) and act as T1-weighted magnetic resonance (MR) imaging contrast agents. Further, the main focus was improving tumor site-specific bioavailability and achieving therapeutic effects through the biocompatibility and biodegradability of Fe@POS-DOX NPs. The Fe@POS-DOX treatment exhibited excellent antitumor effects.Conclusion: Upon intravenous injection, Fe@POS-DOX delivers DOX specifically to the tumor tissues, as revealed by MR, and leads to the inhibition of tumor growth without overt toxicity to normal tissues, thus displaying considerable potential for use in clinical applications.Graphical Abstract: Keywords: poly (α-amino acid)s, polypeptides, polypeptoids, MRI, chemotherapy, nanoparticles
