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WIREs Nanomed Nanobiotechnol
Impact Factor: 9.182

Novel nanomaterial–organism hybrids with biomedical potential

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Abstract 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
Direct combination of organisms and mineral shells. (a) Schematic diagram illustrating direct deposition of calcium phosphate (CaP) on the surface of a mammalian virus. (Reproduced with permission from X. Wang et al., copyright 2017 Royal Society of Chemistry). (b) Structure of zeolite imidazolate framework‐8 (ZIF‐8) assembled from Zn and 2‐methylimidazole (HMIM). (c) Representation of an enzyme encapsulated in ZIF‐8 crystal. (d) Various types of ZIF‐8 crystals formed by interaction of tobacco mosaic virus (TMV) and Zn. (Reproduced with permission from S. Li et al., copyright 2018 American Chemical Society)
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Opportunities (inner loop) and challenges (outer loop) of novel nanomaterial–organic hybrids in biomedical applications
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Schematic diagram of biomineralized vaccine nanohybrids for nasal administration. (Reproduced with permission from X. Wang et al., copyright 2016 Elsevier)
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The CaP modification of the virus disguises the vaccine surface. (a) Schematic diagram of CaP‐mediated prevention of antibody‐dependent enhancement (ADE) of the dengue virus (DENV) infection. (Reproduced with permission from X. Wang et al., copyright 2017 Royal Society of Chemistry). (b) On‐demand immune escape of human adenovirus serotype 5 (Ad5) coated with CaP shell. (Reproduced with permission from X. Wang et al., copyright 2016 Wiley‐VCH)
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Comparison of the bioactivity and thermostability of Japanese encephalitis virus (JEV) and biomimetic mineralized JEV (B‐JEV). (a) Immunofluorescence assays (IFA) of viral protein entry into the cells; JEV‐specific antibody (green) and BHK‐21 cell nuclei (blue). (b) Single‐step growth curves of the viruses in BHK‐21 cells. (c) Plaque formation assays in JEV‐ and B‐JEV‐infected BHK‐21 cells. (d) Comparison of the thermostability of the virus before and after mineralization. (Reproduced with permission from G. Wang et al., copyright 2012 Wiley‐VCH)
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Drug targeting based on exosome (EV) encapsulation and protection of normal cells by implantation of artificial organelles in tumor chemotherapy (TA: tannic acid). (a) Schematic diagram of EV encapsulation and enhanced tolerance of surface‐protected EVs ([email protected][TA‐Fe3+]) to UA‐C irradiation (b) and heat (c). (d) Regulated process of cargo release on demand by a pH‐responsive plasmonic switch. (e) the effect of folic acid (FA)‐modified [email protected][TA‐Fe3+]DOX (FA‐[email protected][TA‐Fe3+]DOX) on MCF‐7 (cancer cells) and CCD1058SK (normal cells). (Reproduced with permission from Kumar et al., copyright 2018 WILEY‐VCH). (f) Working principle of the gold‐oligonucleotide‐doxorubicin (Au‐ODN‐DOX) nanocomposite as a nanomaterial‐based organelle. (g) The mean concentration of Au‐ODN in each organ after the injection. (h) Distribution of Au‐ODN in various organs. (i) Tumor volume and weight of mice subjected to various treatment regimens. (Reproduced with permission from R. Zhao et al., copyright 2018 Wiley‐VCH)
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(a) Scanning electron microscopy (SEM) and confocal imaging characterization of cancer cell‐targeted calcification (CCTC). (b) Comparison of the effects of CCTC on cell viability. (c and d) in vivo experiments confirmed the antitumor effect of CCTC. (Reproduced with permission from R. Zhao et al., copyright 2016 Wiley‐VCH)
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Intracellular characterization of EPI‐siRNA‐CaP. (a–d) Flow cytometry analysis shows that epirubicin (EPI) and siRNAFAM are coencapsulated in CaP nanoparticles; (a) CaP alone, (b) EPI‐CaP, and (c) siRNAFAM–CaP (FAM: 5‐carboxyfluorescein). (e–g) Endocellular distribution of EPI and FAM‐siRNA at various time points after EPI‐siRNA‐CaP treatment. Nucleus, blue fluorescence (upper left, stained with 4′,6‐diamidino‐2‐phenylindole); EPI emission, red fluorescence (upper right); FAM emission, green fluorescence (lower left); merged image (lower right). (Reproduced with permission from W. Chen et al., copyright 2015 Wiley‐VCH)
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Construction of universal red blood cells (RBCs) by a rational surface crosslinking framework. (a) Schematic diagram of RBC surface engineering. (b) Analysis and comparison of the oxygen dissociation curves (ODC), Hill plot, and contents of 2,3‐diphosphoglycerate (2,3‐DPG) and adenosine triphosphate (ATP) of native (black) and engineered RBCs (red). (c) Comparison of the oxyhemoglobin levels in various organs after blood transfusion of native (control, C) and engineered RBCs (E). (d) Survival curve of RBCs after blood transfusion in vivo. (Reproduced with permission from Y. Zhao et al., copyright 2020 American Association for the Advancement of Science)
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Schematic diagram of yeast cell mineralization mediated by bridge polymer, poly(ethyleneimine) (PEI) (YeastWT: wild‐type yeast; YeastECP: encapsulated yeast; PN: poly(norepinephrine); TEOS: tetraethyl orthosilicate) (a) (Reproduced with permission from D. Hong et al., copyright 2015 Royal Society of Chemistry) and polypeptide R4C12R4 (R: arginine; C: cysteine) (b) (Reproduced with permission from J. H. Park et al., copyright 2015 Royal Society of Chemistry)
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Protection of living yeast cells by MOF encapsulation. (a) Biomimetic mineralization of ZIF‐8 on yeast cells. (b) Viability (%) of native yeasts (blue), native yeasts with free ZIF‐8 particles (patterned blue) treated in the presence of the cell lysis enzyme lyticase for 3 h, and ZIF‐8‐coated yeasts treated in the presence of lyticase for 3 h (red) and 24 h (patterned red). (c) Yeast growth (OD600) of various groups before and after the removal of MOF in EDTA solution. (Reproduced with permission from Liang et al., copyright 2016 Wiley‐VCH). (d) Construction and removal of the bioactive porous (β‐gal/ZIF‐8) shell for synthetically adaptive cell survival. (e) Comparison of relative cell viability (%) in an oligotrophic environment. (Reproduced with permission from Liang et al., copyright 2017 Wiley‐VCH)
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Genetic engineering‐mediated external and internal mineralization. (a) Insertion of mineralization‐related peptide in human enterovirus type 71 (EV71). (b) Illustration of the formation of the CaP exterior on the viral surface. (Reproduced with permission from G. Wang et al., copyright 2013 National Academy of Science)
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Two models of internal mineralization: (a) Ion internalization. (Reproduced with permission from X. Ma et al., copyright 2018 Royal Society of Chemistry); (b) Spatial constraints. (Reproduced with permission from T. Douglas et al., copyright 1998 Springer Nature)
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Schematic diagram of polyelectrolyte‐enhanced mineralization. (a) Artificial introduction of a CaP shell on a yeast cell. (Reproduced with permission from B. Wang et al., copyright 2008 Wiley‐VCH). (b) Surface mineralization patterns of cell walls in various organisms. (Reproduced with permission from Y. Wei et al., copyright 2020 Elsevier). (c) The process of coating of cyanobacteria with silicon. (Reproduced with permission from W. Xiong et al., copyright 2013 Royal Society of Chemistry)
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Therapeutic Approaches and Drug Discovery > Nanomedicine for Infectious Disease
Therapeutic Approaches and Drug Discovery > Nanomedicine for Oncologic Disease
Implantable Materials and Surgical Technologies > Nanomaterials and Implants

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