Instinctive hierarchically biomineralized structures of various organisms, such as eggs, algae, and magnetotactic bacteria, afford extra protection and distinct performance, which endow fragile organisms with a tenacious ability to adapt and survive. However, spontaneous formation of hybrid materials is difficult for most organisms in nature. Rapid development of chemistry and materials science successfully obtained the combinations of organisms with nanomaterials by biomimetic mineralization thus demonstrating the reproduction of the structures and functions and generation of novel functions that organisms do not possess. The rational design of biomaterial-organism hybridization can control biological recognition, interactions, and metabolism of the organisms. Thus, nanomaterial-organism hybrids represent a next generation of organism engineering with great potential biomedical applications. This review summarizes recent advances in material-directed organism engineering and is mainly focused on biomimetic mineralization technologies and their outstanding biomedical applications. Three representative types of biomimetic mineralization are systematically introduced, including external mineralization, internal mineralization, and genetic engineering mineralization. The methods involving hybridization of nanomaterials and organisms based on biomimetic mineralization strategies are described. These strategies resulted in applications of various nanomaterial-organism hybrids with multiplex functions in cell engineering, cancer treatment, and vaccine improvement. Unlike classical biological approaches, this material-based bioregulation is universal, effective, and inexpensive. In particular, instead of traditional medical solutions, the integration of nanomaterials and organisms may exploit novel strategies to solve current biomedical problems. This article is categorized under: Implantable Materials and Surgical Technologies > Nanomaterials and Implants Therapeutic Approaches and Drug Discovery > Nanomedicine for Oncologic Disease Therapeutic Approaches and Drug Discovery > Nanomedicine for Infectious Disease.

Novel nanomaterial-organism hybrids with biomedical potential.

Nanotechnological developments, including fabrication and use of magnetic nanomaterials, are growing at a fast pace. Magnetic nanoparticles are exciting tools for use in healthcare, biological sensors, and environmental remediation. Due to better control over final-product characteristics and cleaner production, biogenic nanomagnets are preferable over synthetic ones for technological use. In this sense, the technical requirements and economic factors for setting up industrial production of magnetotactic bacteria (MTB)-derived nanomagnets were studied in the present work. Magnetite fabrication costs in a single-stage fed-batch and a semicontinuous process were US$ 10,372 and US$ 11,169 per kilogram, respectively. Depending on the variations of the production process, the minimum selling price for biogenic nanomagnets ranged between US$ 21 and US$ 120 per gram. Because these prices are consistently below commercial values for synthetic nanoparticles, we suggest that microbial production is competitive and constitutes an attractive alternative for a greener manufacturing of magnetic nanoparticles nanotools with versatile applicability.

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Why Does Not Nanotechnology Go Green? Bioprocess Simulation and Economics for Bacterial-Origin Magnetite Nanoparticles.

Jonghoon Choi João F.Mano Nanotechnology has enabled the development of cutting-edge applications in the fields of biotechnology and bioengineering. Such an impact has emerged in a plethora of technologies and devices targeted at more effective disease diagnosis, monitoring, and treatment. In this special issue, nanostructured materials in different shapes and assembly scales are suggested for healthcare applications. Zhou et al. provide a review of recent advances in the fabrication of flexible sensors taking advantage of functional nanomaterials.[1] Kargozar et al. provide a review on the role of quantum dots, with a focus on in vitro and in vivo studies, as well as a discussion about the clinical translation of these structures.[2] Increasing the focus on the therapeutic potential of nanomaterials, the requests for the development of biocompatible devices for tissue regeneration or replacement are investigated by Raut et al.[3] Discussion on tissue regeneration continues with a review by Abdollahiyan et al. on printing technologies to regenerate the osteochondral interface,[4] as well as with the report by Tolba et al. on amorphous inorganic nanoparticles capable of improving selfhealing properties of both construction and medical cements.[5] Besides their promising role as pro-regenerative units, nanomaterials have also gained momentum as tools to treat tumors. Correia et al. evidenced the importance of using biomimetic 3D cellular aggregates as in vitro tumor models by studying the role of sulfobetaine methacrylate functionalized nanoparticles as enablers of combined photochemotherapy.[6] Peptidebased nanomaterials are also highlighted in this special issue by Deso et al., who addressed multi-layered nanocomposites for near-infrared light-triggered release of drugs to treat breast cancer.[7] Finally, the rising field of immunoengineering is addressed by Demircan et al. through the development of antigenpresenting self-assembled peptides with the potential to be used as vaccines for viral infections or to target cancer cells.[8] Cui et al. review self-assembled nanoparticles as platforms for vaccine development.[9] Also, the preparation of nanostructures through self-assembly and engineering of natural substances such as peptides, magnetosomes, and exosomes is introduced,[10–12] In these reports, the successful fabrication of nanovesicles with better affinity and stability for cancer cell targets is suggested with magnetic reactivity or tissue-regeneration potential. Another example is the use of the physalis mottle virus nanoparticles for intelligent delivery of an anti-cancer drug.[13] There are reports on siRNA delivery using artificial nanostructures and cellulose nanocomposite synthesis techniques in Parkinson’s disease research.[14,15] Those stud-

https://onlinelibrary.wiley.com/doi/pdf/10.1002/biot.202170053

Nanomaterials for Biomedical Applications.

Nanoparticle research has greatly benefitted medical imaging platforms by generating new signals, enhancing detection sensitivity, and expanding both clinical and preclinical applications. For magnetic resonance imaging, the fabrication of superparamagnetic iron oxide nanoparticles has provided a means of detecting cells and has paved the way for magnetic particle imaging. As the field of molecular imaging grows and enables the tracking of cells and their molecular activities so does the possibility of tracking genetically programmed biomarkers. This chapter discusses the advantages and challenges of gene-based contrast, using the bacterial magnetosome model to highlight the requirements of in vivo iron biomineralization and reporter gene expression for magnetic resonance signal detection. New information about magnetosome protein interactions in non-magnetic mammalian cells is considered in the light of design and application(s) of a rudimentary magnetosome-like nanoparticle for molecular imaging. Central to this is the hypothesis that a magnetosome root structure is defined by essential magnetosome genes, whose expression positions the biomineral in a given membrane compartment, in any cell type. The use of synthetic biology for programming multi-component structures not only broadens the scope of reporter gene expression for molecular MRI but also facilitates the tracking of cell therapies.

/pdf/molecular-imaging-with-genetically-programmed-nanoparticles-4e1yehc9md.pdf

Molecular Imaging with Genetically Programmed Nanoparticles

Nanoparticle research has greatly benefitted medical imaging platforms by generating new signals, enhancing detection sensitivity, and expanding both clinical and preclinical applications. For magnetic resonance imaging, the fabrication of superparamagnetic iron oxide nanoparticles has provided a means of detecting cells and has paved the way for magnetic particle imaging. As the field of molecular imaging grows and enables the tracking of cells and their molecular activities so does the possibility of tracking genetically programmed biomarkers. This chapter discusses the advantages and challenges of gene-based contrast, using the bacterial magnetosome model to highlight the requirements of in vivo iron biomineralization and reporter gene expression for magnetic resonance signal detection. New information about magnetosome protein interactions in non-magnetic mammalian cells is considered in the light of design and application(s) of a rudimentary magnetosome-like nanoparticle for molecular imaging. Central to this is the hypothesis that a magnetosome root structure is defined by essential magnetosome genes, whose expression positions the biomineral in a given membrane compartment, in any cell type. The use of synthetic biology for programming multi-component structures not only broadens the scope of reporter gene expression for molecular MRI but also facilitates the tracking of cell therapies. 

Integration of a large-sized DNA fragment into a chromosome is an important strategy for characterization of cellular functions in microorganisms. Magnetotactic bacteria synthesize intracellular organelles comprising membrane-bound single crystalline magnetite, also referred to as magnetosomes. Magnetosomes have gained interest in both scientific and engineering sectors as they can be utilized as a material for biomedical and nanotechnological applications. Although genetic engineering of magnetosome biosynthesis mechanism has been investigated, the current method requires cumbersome gene preparation processes. Here, the chromosomal integration of a plasmid containing ≈27 magnetosome genes (≈26 kbp region) in a non-magnetic mutant of Magnetospirillum magneticum AMB-1 using a broad-host-range plasmid is shown. The genome sequencing of gene-complemented strains reveals the chromosomal integration of the plasmid with magnetosome genes at a specific site, most likely by catalysis of an endogenous transposase. Magnetosome production is successfully enhanced by integrating a variation of magnetosome gene operons in the chromosome. This chromosomal integration mechanism will allow the design of functional magnetosomes de novo and M. magneticum AMB-1 may be used as a chassis for the designed magnetosome production.

Mayu Goto

Papers

Restoration and Modification of Magnetosome Biosynthesis by Internal Gene Acquisition in a Magnetotactic Bacterium.