Synthetic Biohybrids of Red Blood Cells and Cascaded-Enzymes@ Metal-Organic Frameworks for Hyperuricemia Treatment.

Hyperuricemia, caused by an imbalance between the rates of production and excretion of uric acid (UA), may greatly increase the mortality rates in patients with cardiovascular and cerebrovascular diseases. Herein, for fast-acting and long-lasting hyperuricemia treatment, armored red blood cell (RBC) biohybrids, integrated RBCs with proximal, cascaded-enzymes of urate oxidase (UOX) and catalase (CAT) encapsulated within ZIF-8 framework-based nanoparticles, have been fabricated based on a super-assembly approach. Each component is crucial for hyperuricemia treatment: 1) RBCs significantly increase the circulation time of nanoparticles; 2) ZIF-8 nanoparticles-based superstructure greatly enhances RBCs resistance against external stressors while preserving native RBC properties (such as oxygen carrying capability); 3) the ZIF-8 scaffold protects the encapsulated enzymes from enzymatic degradation; 4) no physical barrier exists for urate diffusion, and thus allow fast degradation of UA in blood and neutralizes the toxic by-product H2 O2 . In vivo results demonstrate that the biohybrids can effectively normalize the UA level of an acute hyperuricemia mouse model within 2 h and possess a longer elimination half-life (49.7 ± 4.9 h). They anticipate that their simple and general method that combines functional nanomaterials with living cell carriers will be a starting point for the development of innovative drug delivery systems.

Long-term whole blood DNA preservation by cost-efficient cryosilicification.

Deoxyribonucleic acid (DNA) is the blueprint of life, and cost-effective methods for its long-term storage could have many potential benefits to society. Here we present the method of in situ cryosilicification of whole blood cells, which allows long-term preservation of DNA. Importantly, our straightforward approach is inexpensive, reliable, and yields cryosilicified samples that fulfill the essential criteria for safe, long-term DNA preservation, namely robustness against external stressors, such as radical oxygen species or ultraviolet radiation, and long-term stability in humid conditions at elevated temperatures. Our approach could enable the room temperature storage of genomic information in book-size format for more than one thousand years (thermally equivalent), costing only 0.5 $/person. Additionally, our demonstration of 3D-printed DNA banking artefacts, could potentially allow 'artificial fossilization'.

Robust and Long-Term Cellular Protein and Enzymatic Activity Preservation in Biomineralized Mammalian Cells.

Preservation of evolved biological structure and function in robust engineering materials is of interest for storage of biological samples before diagnosis and development of vaccines, sensors, and enzymatic reactors and has the potential to avoid cryopreservation and its associated cold-chain issues. Here, we demonstrate that "freezing cells in amorphous silica" is a powerful technique for long-term preservation of whole mammalian cell proteomic structure and function at room temperature. Biomimetic silicification employs the crowded protein microenvironment of mammalian cells as a catalytic framework to proximally transform monomeric silicic acid into silicates forming a nanoscopic silica shell over all biomolecular interfaces. Silicification followed by dehydration preserves and passivates proteomic information within a nanoscale thin silica coating that exhibits size selective permeability (<3.6 nm), preventing protein leaching and protease degradation of cellular contents, while providing access of small molecular constituents for cellular enzymatic reaction. Exposure of dehydrated silicified cells to mild etchant or prolonged hydrolysis removes the silica, completely rerevealing biomolecular components and restoring their accessibility and functionality.

Bioinspired Cell Silicification: From Extracellular to Intracellular.

In nature, biosilicification directs the formation of elaborate amorphous silica exoskeletons that provide diatoms mechanically strong, chemically inert, non-decomposable silica armor conferring chemical and thermal stability as well as resistance to microbial attack, without changing the optical transparency or adversely effecting nutrient and waste exchange required for growth. These extraordinary silica/cell biocomposites have inspired decades of biomimetic research aimed at replication of diatoms' hierarchically organized exoskeletons, immobilization of cells or living organisms within silica matrices and coatings to protect them against harmful external stresses, genetic re-programming of cellular functions by virtue of physico-chemical confinement within silica, cellular integration into devices, and endowment of cells with non-native, abiotic properties through facile silica functionalization. In this Perspective, we focus our discussions on the development and concomitant challenges of bioinspired cell silicification ranging from "cells encapsulated within 3D silica matrices" and "cells encapsulated within 2D silica shells" to extra- and intracellular silica replication, wherein all biomolecular interfaces are encased within nanoscopic layers of amorphous silica. We highlight notable examples of advances in the science and technology of biosilicification and consider challenges to advancing the field, where we propose cellular "mineralization" with arbitrary nanoparticle exoskeletons as a generalizable means to impart limitless abiotic properties and functions to cells, and, based on the interchangeability of water and silicic acid and analogies between amorphous ice and amorphous silica, we consider "freezing" cells within amorphous silica as an alternative to cryo-preservation.

Artificial Bioaugmentation of Biomacromolecules and Living Organisms for Biomedical Applications.

The synergistic union of nanomaterials with biomaterials has revolutionized synthetic chemistry, enabling the creation of nanomaterial-based biohybrids with distinct properties for biomedical applications. This class of materials has drawn significant scientific interest from the perspective of functional extension via controllable coupling of synthetic and biomaterial components, resulting in enhancement of the chemical, physical, and biological properties of the obtained biohybrids. In this review, we highlight the forefront materials for the combination with biomacromolecules and living organisms and their advantageous properties as well as recent advances in the rational design and synthesis of artificial biohybrids. We further illustrate the incredible diversity of biomedical applications stemming from artificially bioaugmented characteristics of the nanomaterial-based biohybrids. Eventually, we aim to inspire scientists with the application horizons of the exciting field of synthetic augmented biohybrids.

Advanced Nanomaterials-Assisted Cell Cryopreservation: A Mini Review.

Cell cryopreservation is of vital significance both for transporting and storing cells before experimental/clinical use. Cryoprotectants (CPAs) are necessary additives in the preserving medium in cryopreservation, preventing cells from freeze-thaw injuries. Traditional organic solvents have been widely used in cell cryopreservation for decades. Given the obvious damage to cells due to their undesirable cytotoxicity and the burdensome post-thaw washing cycles before use, traditional CPAs are more and more likely to be replaced by modern ones with lower toxicity, less processing, and higher efficiency. As materials science thrives, nanomaterials are emerging to serve as potent vehicles for delivering nontoxic CPAs or inherent CPAs comparable to or even superior to conventional ones. This review will introduce some advanced nanomaterials (e.g., organic/inorganic nanoCPAs, nanodelivery systems) utilized for cell cryopreservation, providing broader insights into this developing field.