Organic-inorganic covalent-ionic molecules for elastic ceramic plastic.

Although organic-inorganic hybrid materials have played indispensable roles as mechanical1-4, optical5,6, electronic7,8 and biomedical materials9-11, isolated organic-inorganic hybrid molecules (at present limited to covalent compounds12,13) are seldom used to prepare hybrid materials, owing to the distinct behaviours of organic covalent bonds14 and inorganic ionic bonds15 in molecular construction. Here we integrate typical covalent and ionic bonds within one molecule to create an organic-inorganic hybrid molecule, which can be used for bottom-up syntheses of hybrid materials. A combination of the organic covalent thioctic acid (TA) and the inorganic ionic calcium carbonate oligomer (CCO) through an acid-base reaction provides a TA-CCO hybrid molecule with the representative molecular formula TA2Ca(CaCO3)2. Its dual reactivity involving copolymerization of the organic TA segment and inorganic CCO segment generates the respective covalent and ionic networks. The two networks are interconnected through TA-CCO complexes to form a covalent-ionic bicontinuous structure within the resulting hybrid material, poly(TA-CCO), which unifies paradoxical mechanical properties. The reversible binding of Ca2+-CO32- bonds in the ionic network and S-S bonds in the covalent network ensures material reprocessability with plastic-like mouldability while preserving thermal stability. The coexistence of ceramic-like, rubber-like and plastic-like behaviours within poly(TA-CCO) goes beyond current classifications of materials to generate an 'elastic ceramic plastic'. The bottom-up creation of organic-inorganic hybrid molecules provides a feasible pathway for the molecular engineering of hybrid materials, thereby supplementing the classical methodology used for the manufacture of organic-inorganic hybrid materials.

Smart Nanosacrificial Layer on the Bone Surface Prevents Osteoporosis through Acid-Base Neutralization Regulated Biocascade Effects.

Osteoporosis is a global chronic disease characterized by severe bone loss and high susceptibility to fragile fracture. It is widely accepted that the origin acidified microenvironment created by excessive osteoclasts causes irreversible bone mineral dissolution and organic degradation during osteoclastic resorption. However, current clinically available approaches are mainly developed from the perspective of osteoclast biology rather than the critical acidified niche. Here, we developed a smart "nanosacrificial layer" consisting of sodium bicarbonate (NaHCO3)-containing and tetracycline-functionalized nanoliposomes (NaHCO3-TNLs) that can target bone surfaces and respond to external secreted acidification from osteoclasts, preventing osteoporosis. In vitro and in vivo results prove that this nanosacrificial layer precisely inhibits the initial acidification of osteoclasts and initiates a chemically regulated biocascade to remodel the bone microenvironment and realize bone protection: extracellular acid-base neutralization first inhibits osteoclast function and also promotes its apoptosis, in which the apoptosis-derived extracellular vesicles containing RANK (receptor activator of nuclear factor-κ B) further consume RANKL (RANK ligand) in serum, achieving comprehensive osteoclast inhibition. Our therapeutic strategy for osteoporosis is based on original and precise acid-base neutralization, aiming to reestablish bone homeostasis by using a smart nanosacrificial layer that is able to induce chemically regulated biocascade effects. This study also provides a novel understanding of osteoporosis therapy in biomedicine and clinical treatments.

Anisotropic Epitaxial Behavior in the Amorphous Phase-Mediated Hydroxyapatite Crystallization Process: A New Understanding of Orientation Control.

The precise control of crystallization is a key in the construction and engineering of crystalline materials, especially in biomineralization. Although it is generally accepted that biomineral crystals have evolved from their amorphous precursors, there are intense debates about crystallographic orientation control. By using in situ high-resolution transmission electron microscopy, we herein reveal that hydroxyapatite (HAP) is produced through its epitaxial growth from amorphous calcium phosphate with a preferential c-axis orientation. Abnormally but interestingly, this anisotropic epitaxial crystallization priority along the c-axis is not affected by the existing HAP crystalline substrate, which is exactly the same on either {002} or {100} facets. Molecular dynamics simulations suggest this preference is correlated with the interfacial energetic controls at the amorphous-crystalline transition frontier. The orientation control of biominerals here shows the key role of the interface energy, rather that the organic molecules or matrices, which provides a complementary understanding of the general c-axis orientation control of HAP in various biomineralization cases and aids in the development of an alternative strategy for crystallization control of functional materials.

Biomineralization improves the thermostability of foot-and-mouth disease virus-like particles and the protective immune response induced.

Virus-like particles (VLPs) are an ideal substitute for traditionally inactivated or attenuated viruses in vaccine production. However, given the properties of their native proteins, the thermal stability of VLPs is poor. In this study, calcium mineralization was used to fabricate foot-and-mouth disease virus (FMDV) VLPs as immunogenic core-shell particles with improved thermal stability. The biomineralized VLPs were stably stored at 24 °C and 37 °C for 13 and 11 days, respectively. Animal experiments showed that the biomineralized VLPs induced specific protective immunogenic effects, even after storage at 37 °C for 7 days. The biomineralized VLPs also effectively activated dendritic cells (DCs) to express high levels of surface MHC-II, costimulatory molecules, and proinflammatory cytokines. The DCs activated by the mineralized VLPs rapidly localized to the secondary lymphoid tissues and promoted the activation of the native T-cell population. These results suggest that the biomineralization of VLPs is an effective approach to vaccine production insofar as the mineralized shell provides an adjuvant effect which improves the immunogenicity of the VLPs. Biomineralization can also confer superior heat resistance on VLPs, an advantage in vaccine production. The successful development of thermally stable, biomineralized VLPs will reduce our dependence on cold storage and delivery.

Alumina-encapsulated vaccine formulation with improved thermostability and immunogenicity.

Developing vaccine formulations with excellent thermostability and immunogenicity remains a great challenge. By in situ encapsulating a live-attenuated strain of human enterovirus 71 (EV71) in alumina, we obtained a robust vaccine formulation named EV71@NanoAlum, which features significantly enhanced thermostability and immunogenicity. This attempt follows a material-based tactic for vaccine improvement.

Spindle-like polypyrrole hollow nanocapsules as multifunctional platforms for highly effective chemo-photothermal combination therapy of cancer cells in vivo.

The monodispersed spindle-like polypyrrole hollow nanocapsules (PPy HNCs) as the multifunctional platforms for combining chemotherapy with photothermal therapy for cancer cells are reported. Whereas the hollow cavity of nanocapsules can be used to load the anticancer drug (i.e., doxorubicin) for chemotherapy, the PPy shells can convert NIR light into heat for photothermal therapy. The release of the drug from the spindle-like PPy HNCs is pH-sensitive and near-infrared (NIR) light-enhanced. More importantly, the spindle-like PPy HNCs can penetrate cells more rapidly and efficiently in comparison with the spherical PPy HNCs. Both in vitro and in vivo experiments demonstrated that the combination of DOX-loaded spindle-like PPy HNCs and NIR light provide a highly effective and feasible chemo-photothermal therapy cancer method with a synergistic effect. Owing to their high photothermal conversion efficiency, large hollow cavity, and good biocompatibility, the spindle-like PPy HNCs could be used as a promising new cancer drug-nanocarrier and photothermal agent for localized tumorous chemo-photothermal therapy.