Design and Preparation of “corn-like” SPIONs@DFK-SBP-M13 Assembly for Improvement of Effective Internalization

Abstract

Na Zhang,1,* Hui Wu,2,* Yingzhi Liang,1,* Jianming Ye,1 Huan Zhang,3 Yuqing Miao,3 Yane Luo,1 Haiming Fan,3 Tianli Yue1,4 1College of Food Science and Technology, Northwest University, Xi’an, Shaanxi, 710069, People’s Republic of China; 2State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, Shanghai, 200237, People’s Republic of China; 3Key Laboratory of Synthetic and Natural Functional Molecule Chemistry of the Ministry of Education, College of Chemistry and Materials Science, Northwest University, Xi’an, Shaanxi, 710069, People’s Republic of China; 4Laboratory of Quality and Safety Risk Assessment for Agro-Products (Yangling), Ministry of Agriculture, Beijing, People’s Republic of China*These authors contributed equally to this workCorrespondence: Yane Luo Email [email protected]: Superparamagnetic iron oxide nanoparticles (SPIONs) have exhibited preeminent diagnosis and treatment performances, but their low internalization severely limits predesigned functions. The low cell internalization is now an urgent bottleneck problem for almost all nanomaterials. To achieve more internalization of SPIONS, recombinant M13 phage was designed for targeted delivery and smart release.Methods: M13 phages were designed to co-express exogenous SPARC binding peptide (SBP) and cathepsin B cleavage peptide (DFK), formed recombinant DFK-SBP-M13. 3.37± 0.06 nm of SPIONs were modified by 3, 4-dihydroxyhydrocinnamic acid (DHCA) to gain 10.80 ± 0.21 nm of DHCA-coated SPIONs, i.e., DHCA@SPIONs. Upon adjusting the proportions of DHCA@SPIONs and DFK-SBP-M13, the multi-carboxyl SPIONs assembled onto recombinant M13 phages via covalent bonding. The assemblies were co-cultured with MDA-MB-231 cells to interpret their internalization and smart release.Results: The “corn-like” SPIONs@DFK-SBP-M13 (261.47± 3.30 nm) assemblies have not been reported previously. The assembly was stable, dispersible, superparamagnetic and biocompatible. After co-cultivation with MDA-MB-231 cells, the SPIONs@DFK-SBP-M13 assemblies quickly bond to the cell surface and are internalized. The enrichment rate of SPIONs@DFK-SBP-M13 assembly was 13.9 times higher than free SPIONs at 0.5 h, and intracellular Fe content was 3.6 times higher at 1 h. Furthermore, the DFK peptides favored cathepsin B to cleave SPIONs from the M13 templates resulting in release of SPIONs inside cells.Conclusion: The novel SPIONs@DFK-SBP-M13 assembly can rapidly deliver SPIONs to the targeted sites and enabled smart release. The combination of genetic recombination and nanotechnology is beneficial for designing and optimizing some new nanomaterials with special functions to achieve wider applications.Keywords: M13 phage, superparamagnetic iron oxide nanoparticles, self-assembly, smart release, targeting

Keywords

• m13 phage
• superparamagnetic iron oxide nanoparticles
• self-assembly
• smart release
• targeting