Alteration of Young's modulus in mesenchymal stromal cells during osteogenesis measured by atomic force microscopy.

Mechanical properties of biological tissues are increasingly recognized as an important parameter for the indication of disease states as well as tissue homeostasis and regeneration. Multipotent mesenchymal stromal/stem cells (MSCs), which play important roles in bone formation and remodeling, are potential cell sources for regenerative medicine. However, the cellular mechanical properties of differentiating MSCs corresponding to the substrate stiffness has not been sufficiently studied. In this study, we used Atomic Force Microscopy (AFM) to measure changes of stiffness of human MSCs cultured in rigid Petri dish and on polyacrylamide (PA) substrates during osteogenic differentiation. The results showed that the Young's modulus of MSC cytoplasmic outer region increased over time during osteogenesis. There is a strong linear correlation between the osteogenic induction time and the Young's modulus of the cells cultured in rigid Petri dishes in the first 15 days after the induction; the Young's modulus approaches to a plateau after day 15. On the other hand, the Young's moduli of MSCs cultured on PA gels with stiffness of 7 kPa and 42 kPa also increase over time during osteogenic differentiation, but the inclination of such increase is much smaller than that of MSCs differentiating in rigid dishes. Herein, we established a protocol of AFM measurement to evaluate the maturation of stem cell osteogenic differentiation at the single cell level and could encourage further AFM applications in tissue engineering related to mechanobiology.

Doxorubicin-loaded star-shaped copolymer PLGA-vitamin E TPGS nanoparticles for lung cancer therapy.

A doxorubicin-loaded mannitol-functionalized poly(lactide-co-glycolide)-b-D-α-tocopheryl polyethylene glycol 1000 succinate nanoparticles (DOX-loaded M-PLGA-b-TPGS NPs) were prepared by a modified nanoprecipitation method. The NPs were characterized by the particle size, surface morphology, particle stability, in vitro drug release and cellular uptake efficiency. The NPs were near-spherical with narrow size distribution. The size of M-PLGA-b-TPGS NPs was ~110.9 nm (much smaller than ~143.7 nm of PLGA NPs) and the zeta potential was -35.8 mV (higher than -42.6 mV of PLGA NPs). The NPs exhibited a good redispersion since the particle size and surface charge hardly changed during 3-month storage period. In the release medium (phosphate buffer solution vs. fetal bovine serum), the cumulative drug release of DOX-loaded M-PLGA-b-TPGS, PLGA-b-TPGS, and PLGA NPs were 76.41 versus 83.11 %, 58.94 versus 73.44 % and 45.14 versus 53.12 %, respectively. Compared with PLGA-b-TPGS NPs and PLGA NPs, the M-PLGA-b-TPGS NPs possessed the highest cellular uptake efficiency in A549 and H1975 cells (lung cancer cells). Ultimately, both in vitro and in vivo antitumor activities were evaluated. The results showed that M-PLGA-b-TPGS NPs could achieve a significantly higher level of cytotoxicity in cancer cells and a better antitumor efficiency on xenograft BALB/c nude mice tumor model than free DOX. In conclusion, the DOX-loaded M-PLGA-b-TPGS could be used as a potential DOX-loaded nanoformulation in lung cancer chemotherapy.

Dissolution-precipitation method concatenated sodium alginate/MOF-derived magnetic multistage pore carbon magnetic solid phase extraction for determination of antioxidants and ultraviolet stabilizers in polylactic acid food contact plastics.

Antioxidants and UV stabilizers have some endocrine disrupting effects and liver toxicity. Both types of additives are still widely used in food contact plastics to improve the durability of plastic products. However, efficient and rapid detection of antioxidants and UV stabilizers has been a challenge due to the complexity of the plastic matrix and the low content of antioxidants and UV stabilizers. In this study, a sodium alginate/MOF-derived magnetic multistage pore carbon material (MIL-101(Fe)/SA-CAs) was developed, having the merits of abundant multistage pore structure, large specific surface area, and good magnetic separation properties. Thus, this material was selected as the sorbent for magnetic solid-phase extraction combined with a dissolution-precipitation method for the extraction and purification of antioxidants and UV stabilizers from polylactic acid food contact plastics. The extraction parameters such as sorbent type, sorbent dosage, sample solution pH, ionic strength, sorption time, elution solution type, volume, and time were investigated. Under the optimized conditions, all the analytes determined by UPLC-MS/MS showed good linear range (r > 0.99), detection limit (0.023-3.105 ng g-1), accuracy (70.6-102.3 %), and reproducibility (RSD<9.8 %). Further, the developed method was applied to determine the antioxidants and UV stabilizers in polylactic acid lunch boxes and straws, showing excellent applicability. The results showed that the antioxidants and UV stabilizers were detected in some of the samples, with a maximum detection of antioxidant 1010 at 7297 ng g-1. This study provided a sensitive, efficient, and environmentally friendly method for antioxidants and UV stabilizers in polylactic acid food contact plastics. The ideas for the design of environmentally friendly metal-organic frameworks and biomass composite multifunctional materials would promise in the sample pretreatment field for the emerging contaminants.

Co-hydrothermal carbonization of polyvinyl chloride and lignocellulose biomasses for chlorine and inorganics removal.

Co-hydrothermal carbonization (co-HTC) of lignocellulose biomass (LB) and chlorinated waste can simultaneously remove organic chlorine and inorganics, however, the interaction mechanisms are unclear owing to the variety of operating conditions and complexity of biomass compositions. Pine, bamboo, corncob, corn stalk, and wheat straw were co-hydrothermally carbonized with polyvinyl chloride (PVC) at the mass ratio of 9:1 for 30 min under 260 °C to explore the fundamental interactions. The synergistic index (SI) of dechlorination efficiency ranged from -20.3 % to 19.9 %, indicating the interaction depended on the content and composition of cellulose, hemicellulose, and lignin in the LB feedstocks. Hydroxyl functional groups in cellulose and soluble lignin dehydration intermediates promoted PVC substitution. The LB fragments prevented PVC aggregation while promoted PVC fragmentation, thereby facilitating dechlorination. The polyaromatic hydrochar derived from insoluble lignin and polymeric hydrochar derived from hemicellulose, cellulose, and soluble lignin can coat the surface of molten PVC and act as significant dechlorination inhibitors. All SI of removal efficiency of inorganics (RE) were positive, ranging from 0.74 % to 154 %, with large variations for different inorganics, indicating that inorganics contents in LB influenced RE significantly. A large amount of water-insoluble/acid-soluble inorganics was removed via a metathesis reaction. Soluble inorganics were dissolved in the process water by HCl leaching.

Insights to the 3D internal morphology and metal oxidation states of single atmospheric aerosol particles by synchrotron-based methodology.

The morphology and metal oxidation states of atmospheric aerosols are pertinent to their formation processes and ensuing interactions with surrounding gases, vapors and other environments upon deposition, such as human respiratory tract, soil and water. Although much progress has been made in recent years through single-particle techniques, considerably less is known with respect to the three-dimensional (3D) internal morphology of single atmospheric aerosol particles due to the limited penetration depth of electron microscopy. In this study, for the first time, a novel synchrotron-based transmission X-ray microscopy (TXM) methodology has been developed to visualize the 3D internal chemical mixing state and structure of single particles. The results show that the TXM is more applicable to the imaging of solid particles containing high-density elements, e.g., iron (Fe), aluminum (Al), silicone (Si), carbon (C) and sulfur (S), and/or solid particles of sizes larger than about 100 nm. In addition, the TXM is capable to reveal the fine 3D topographic features of single particles. The derived 3D internal and external information would be difficult to discern in the 2D images from electron microscopy. The TXM 3D images illustrate that aerosol particles exhibit complex internal mixing state and structure, e.g., homogeneously-, heterogeneously-mixed, multiple inclusions, fibrous, porous, and core-shell configuration. When coupled with the synchrotron-based X-ray fluorescence spectrometry (XRF) and absorption near-edge spectroscopy (XANES) of an X-ray nanoprobe in the energy range of 4-15 keV, the 3D morphology of single particles is further supplemented with the spatial distribution and oxidation sates of selected elements, including Fe, vanadium (V), manganese (Mn), chromium (Cr) and arsenic (As). The presented cross-platform, synchrotron-based methodology shows promise in complementing existing single-particle techniques and providing new insights to the heterogeneity of single-particle micro-physicochemical states relevant to the aerosol chemistry, optical properties, and their environmental and health impacts.

A sandwich-type electrochemical aptasensor for Mycobacterium tuberculosis MPT64 antigen detection using C60NPs decorated N-CNTs/GO nanocomposite coupled with conductive PEI-functionalized metal-organic framework.

The present work described a novel sandwich-type electrochemical aptasensor for rapid and sensitive determination of Mycobacterium tuberculosis MPT64 antigen. Herein, a novel carbon nanocomposite composed of fullerene nanoparticles, nitrogen-doped carbon nanotubes and graphene oxide (C60NPs-N-CNTs/GO) was facilely synthesized for the first time, which not only possessed a large specific surface area and excellent conductivity, but also exhibited outstanding inherent electroactive property, and therefore served as nanocarrier and redox nanoprobe simultaneously. Gold nanoparticles (AuNPs) was then uniformly anchored onto the surface of such nanocomposite via Au-N bonds to bind with MPT64 antigen aptamer Ⅱ (MAA Ⅱ), forming the tracer label to realize generation and amplification of electrochemical signal. Additionally, conductive polyethyleneimine (PEI)-functionalized Fe-based metal-organic framework (P-MOF) was used as a sensing platform to absorb bimetallic core-shell Au-Pt nanoparticles (Au@Pt), which could accelerate electron transfer and increase the immobilization of MPT64 antigen aptamer Ⅰ (MAA Ⅰ). After the typical sandwich-type protein-aptamer recognition, the inherent electroactivity of the tracer label was provoked by tetraoctylammonium bromide (TOAB), leading to a well-defined current response. Under the optimum condition, the proposed aptasensor showed a wide linear range for MPT64 detection from 1 fg/mL to 1 ng/mL with a limit of detection (LOD) as low as 0.33 fg/mL. More importantly, it was successfully used for MPT64 antigen detection in human serum, exhibiting a promising prospect for TB diagnosis in clinical practice.

Polydopamine-based surface modification of mesoporous silica nanoparticles as pH-sensitive drug delivery vehicles for cancer therapy.

A novel pH-sensitive drug delivery system of mesoporous silica nanoparticles (MSNs) which were modified by polydopamine (PDA) for controlled release of cationic amphiphilic drug desipramine (DES) was prepared. MSNs-DES-PDA were characterized in terms of size, size distribution, surface morphology, BET surface area, mesoporous size and pore volume, drug loading content and in vitro drug release profile. MSNs-DES-PDA had high drug loading content and pH sensitivity. The DES release profiles of MSNs-DES and MSNs-DES-PDA were totally different, and the drug release of MSNs-DES-PDA accelerated with increasing acidity. MSNs-DES-PDA can be internalized into cells. In vitro experiments demonstrated that MSNs-DES-PDA had higher cytotoxicity and inhibitory effects on acid sphingomyelinase than those of free DES. This drug delivery system was beneficial for controlled release and cancer therapy.

Nanoformulation of D-α-tocopheryl polyethylene glycol 1000 succinate-b-poly(ε-caprolactone-ran-glycolide) diblock copolymer for siRNA targeting HIF-1α for nasopharyngeal carcinoma therapy.

Hypoxia-inducible factor-1α (HIF-1α) is a crucial transcription factor that plays an important role in the carcinogenesis and development of nasopharyngeal carcinoma. In this research, a novel biodegradable D-α-tocopheryl polyethylene glycol 1000 succinate-b-poly(ε-caprolactone-ran-glycolide) (TPGS-b-(PCL-ran-PGA)) nanoparticle (NP) was prepared as a delivery system for small interfering ribonucleic acid (siRNA) molecules targeting HIF-1α in nasopharyngeal carcinoma gene therapy. The results showed that the NPs could efficiently deliver siRNA into CNE-2 cells. CNE-2 cells treated with the HIF-1α siRNA-loaded TPGS-b-(PCL-ran-PGA) NPs showed reduction of HIF-1α expression after 48 hours of incubation via real-time reverse transcriptase-polymerase chain reaction and Western blot analysis. The cytotoxic effect on CNE-2 cells was significantly increased by HIF-1α siRNA-loaded NPs when compared with control groups. In a mouse tumor xenograft model, the HIF-1α siRNA-loaded NPs efficiently suppressed tumor growth, and the levels of HIF-1α mRNA and protein were significantly decreased. These results suggest that TPGS-b-(PCL-ran-PGA) NPs could function as a promising genetic material carrier in antitumor therapy, including therapy for nasopharyngeal carcinoma.