Long-term Effect of Biomineralized Insulin Nanoparticles on Type 2 Diabetes Treatment.

Intracellular insulin may exhibit a long-term effect in regulating protein synthesis, DNA synthesis, and gene transcription. However, the intracellular delivery of insulin is a great challenge. Here, we describe how a simple biomineralization modification of insulin can transport it into intact cells on a large scale, leading to a long-term therapeutic effect on diabetes mellitus. Using insulin-resistant HepG2 cell and diabetic KKAy mice as models, in vitro and in vivo assessments have demonstrated that biomineralized insulin nanoparticles can trigger glucose metabolism, and this improvement extends after the treatment. The potential exists to improve the current treatment of type 2 diabetes mellitus through biomineralized modifications of insulin. This study provides a new paradigm of biomimetic nanotechnology for biomedical applications.

Protection of Photosynthetic Algae against Ultraviolet Radiation by One-Step CeO2 Shellization.

Photosynthetic microalgae play an important role in solar-to-chemical energy conversion on Earth, but the increasing solar ultraviolet (UV) radiation seriously reduces the biological photosynthesis. Here, we developed a one-step approach to construct cell-in-shell hybrid structure by using direct adsorption of CeO2 nanoparticles onto cells. The engineered CeO2 nanoshell can efficiently protect the enclosed Chlorella cell due to its excellent UV filter property, which can also eliminate UV-induced oxidative stress. The experiments demonstrate that the resulted algae-CeO2 composites can guarantee their biological photosynthetic process and efficiency even under UV. This study follows a feasible strategy to protect living organisms by using functional nanomaterials to improve their biological functions.

Cells Recognize and Prefer Bone-like Hydroxyapatite: Biochemical Understanding of Ultrathin Mineral Platelets in Bone.

Hydroxyapatite (HAP) nanocrystallites in all types of bones are distinguished by their ultrathin characteristics, which are uniaxially oriented with fibrillar collagen to uniquely expose the (100) faces. We speculate that living organisms prefer the specific crystal morphology and orientation of HAP because of the interactions between cells and crystals at the mineral-cell interface. Here, bone-like platy HAP (p-HAP) and two different rod-like HAPs were synthesized to investigate the ultrathin mineral modulating effect on cell bioactivity and bone generation. Cell viability and osteogenic differentiation of mesenchymal stem cells (MSCs) were significantly promoted by the platy HAP with (100) faces compared to rod-like HAPs with (001) faces as the dominant crystal orientation, which indicated that MSCs can recognize the crystal face and prefer the (100) HAP faces. This face-specific preference is dependent on the selective adsorption of fibronectin (FN), a plasma protein that plays a central role in cell adhesion, on the HAP surface. This selective adsorption is further confirmed by molecule dynamics (MD) simulation. Our results demonstrate that it is an intelligent choice for cells to use ultrathin HAP with a large (100) face as a basic building block in the hierarchical structure of bone, which is crucial to the promotion of MSCs osteoinductions during bone formation.

Biomineralized vaccine nanohybrid for needle-free intranasal immunization.

Frequent outbreaks and the rapid global spread of infectious diseases have increased the urgent need for massive vaccination especially in countries with limited resources. Intranasal vaccination facilitates the mass vaccination via needle-free delivery of vaccine through nasal mucosal surfaces. Inspired by the strong capability of calcium phosphate (CaP) materials to adhere to cells and tissues, we propose to improve nasal vaccination by using a biomineralization-based strategy. The vaccine nanohybrid was obtained by covering the viral surface with CaP nanoshell, which changed the physiochemical properties of original vaccine, resulting in the increase of mucosal adhesion to the nasal tissues. The core-shell structure was beneficial for the receptor-independent uptake and the induction of elevated local IgA response within the nasal cavity. Moreover, the vaccine complex elicited enhanced systemic antibody response that neutralized wild type of dengue virus and promoted the systemic cellular immune responses. This achievement presents the potential of CaP based vaccine biomineralization for the fabrication of needle-free vaccine formulation.

Nano regulation of cisplatin chemotherapeutic behaviors by biomineralization controls.

Controllable biomineralization modification of cisplatin can alter the drug biodistribution with extended circulation time in blood. These changes increase passive tumor target and decrease non-specific accumulation significantly, which can improve chemotherapeutic effect with minimum side effects.

Rational design of thermostable vaccines by engineered peptide-induced virus self-biomineralization under physiological conditions.

The development of vaccines against infectious diseases represents one of the most important contributions to medical science. However, vaccine-preventable diseases still cause millions of deaths each year due to the thermal instability and poor efficacy of vaccines. Using the human enterovirus type 71 vaccine strain as a model, we suggest a combined, rational design approach to improve the thermostability and immunogenicity of live vaccines by self-biomineralization. The biomimetic nucleating peptides are rationally integrated onto the capsid of enterovirus type 71 by reverse genetics so that calcium phosphate mineralization can be biologically induced onto vaccine surfaces under physiological conditions, generating a mineral exterior. This engineered self-biomineralized virus was characterized in detail for its unique structural, virological, and chemical properties. Analogous to many exteriors, the mineral coating confers some new properties on enclosed vaccines. The self-biomineralized vaccine can be stored at 26 °C for more than 9 d and at 37 °C for approximately 1 wk. Both in vitro and in vivo experiments demonstrate that this engineered vaccine can be used efficiently after heat treatment or ambient temperature storage, which reduces the dependence on a cold chain. Such a combination of genetic technology and biomineralization provides an economic solution for current vaccination programs, especially in developing countries that lack expensive refrigeration infrastructures.

Overcoming cisplatin resistance in chemotherapy by biomineralization.

Nano-solidified intermedias (NSI) of cisplatin were prepared via biomineralization and applied to reverse the drug resistance of cancers in vitro and in vivo by an alternative internalization pathway.

Biomineralization-based virus shell-engineering: towards neutralization escape and tropism expansion.

Biomineralization-based virus shell-engineering (BVSE) is a potential surface modification strategy to afford a biocompatible and biodegradable calcium phosphate (CaPi) shell onto single virus, allowing development of Trojan virus with enhanced infection, expanded tropism and neutralization escape, which open up the multiple applications of virus in biomedicines and materials.

Preparing nano-calcium phosphate particles via a biologically friendly pathway.

It is widely agreed that nano-calcium phosphates (CaP) play an important role in tissue engineering and medical application due to their unique biological characteristics. However, the properties of nano-CaP, including bioactivity, biocompatibility and mechanical properties, are tailored over wide ranges by controlling the size and morphology of particles. Therefore, it is important to develop synthesis methods which can control the particle size distribution and shape uniformly. In this study, we report that polyacrylic acid (PAA) can act as an efficient agent to modulate nano-CaP formation. The dimension of the resultant sphere-like nanoparticles (5-60 nm) can readily be regulated by changing PAA concentrations (75-200 microg ml(-1)). In contrast to other additives, PAA is a water-soluble polymer that has already been used as an excellent biocompatible implant material in vivo. Our in vitro proliferation experiments of bone marrow mesenchymal stem cells (BMSCs) demonstrate that the involvement of PAA does not change the bioactivity of the resultant nano-CaP. In contrast, the nano-CaP fabricated by using another typical control agent, hexadecyl (cetyl) trimethyl ammonium bromide, suppressed the cell proliferation of BMSCs. Thus, we suggest that the biopolymer, PAA, can provide a more biologically friendly pathway to prepare biological nano-CaP for biomedical application.

Characteristics of nickel doped zinc oxide thin films prepared by sputtering.

Nickel-doped zinc oxide thin films were prepared by the magnetron sputtering method. We have studied the structure and optical properties of the samples by using X-ray diffraction (XRD), scanning electron microscopy (SEM), and optical transmittance. The chemical ingredients were examined by energy dispersive X-ray spectroscopy (EDS), and the charge state of Ni ions in the ZnO:Ni films was characterized by X-ray photoelectronic spectrometry (XPS). From the XRD spectra of the samples, it was obvious that there was no second phase, but the doping can disturb the ZnO crystal lattice and change the lattice parameters. All the films prepared have a wurtzite structure and grow mainly along the c-axis orientation. The magnetic measurments showed that the samples exhibit no ferromagnetism above room temperature.