Mitochondria-Targeted Nanoadjuvants Induced Multi-Functional Immune-Microenvironment Remodeling to Sensitize Tumor Radio-Immunotherapy.

It is newly revealed that collagen works as a physical barrier to tumor immune infiltration, oxygen perfusion, and immune depressor in solid tumors. Meanwhile, after radiotherapy (RT), the programmed death ligand-1 (PD-L1) overexpression and transforming growth factor-ß (TGF-ß) excessive secretion would accelerate DNA damage repair and trigger T cell exclusion to limit RT efficacy. However, existing drugs or nanoparticles can hardly address these obstacles of highly effective RT simultaneously, effectively, and easily. In this study, it is revealed that inducing mitochondria dysfunction by using oxidative phosphorylation inhibitors like Lonidamine (LND) can serve as a highly effective multi-immune pathway regulation strategy through PD-L1, collagen, and TGF-ß co-depression. Then, IR-LND is prepared by combining the mitochondria-targeted molecule IR-68 with LND, which then is loaded with liposomes (Lip) to create IR-LND@Lip nanoadjuvants. By doing this, IR-LND@Lip more effectively sensitizes RT by generating more DNA damage and transforming cold tumors into hot ones through immune activation by PD-L1, collagen, and TGF-ß co-inhibition. In conclusion, the combined treatment of RT and IR-LND@Lip ultimately almost completely suppressed the growth of bladder tumors and breast tumors.

Mineralized Enzyme-Based Biomaterials with Superior Bioactivities for Bone Regeneration.

The formation and metabolic balance of bone tissue is a controllable process of biomineralization, which is regulated by various cells, biomolecules, and ions. Enzyme molecules play an important role in this process, and alkaline phosphatase (ALP) is one of the most critical factors. In this study, inspired by the process of bone biomineralization, a biomimetic strategy is achieved for the preparation of mineralized ALP nanoparticles (MALPNs), by taking advantages of the unique reaction between ALP and calcium ions in Dulbecco's modified Eagle's medium. Benefiting from the mild biomineralization reaction, the MALPN system highly maintains the activity of ALP. Furthermore, the in vitro studies show that the MALPN system significantly enhances the proliferation of bone marrow mesenchymal stem cells and upregulates their osteogenic differentiation. When evaluated as synthetic graft materials for bone regeneration, the MALPN-incorporated gelatin methacryloyl graft shows excellent mechanical properties, a sustained release profile of ALP, and high biocompatibility and efficacy in guiding bone regeneration and vascularization for critical-sized rat calvarial defect. Moreover, we also demonstrate that the biomimetic mineralization strategy can be adopted for other proteins such as acid phosphatase, bovine serum albumin, fibrinogen, and gelatin, suggesting its universality for constructing mineralized protein-/enzyme-based bioactive materials for the application of tissue regeneration.

Composition and bioactivity of calcium phosphate coatings on anodic oxide nanotubes formed on pure Ti and Ti-6Al-4V alloy substrates.

Electronic structure and bioactivity of calcium phosphate (CaP) coatings on Ti-based anodic nanotubes are investigated. Nanotubes on pure Ti and Ti-6Al-4V alloy, respectively, are used as substrates for CaP deposition. The CaP coatings are formed by first growing a seeding CaP layer using alternative immersion (AIM) treatment followed by crystallization in Dulbecco's phosphate-buffered saline (DPBS). CaP coatings formed on both Ti and Ti-6Al-4V substrates are found containing a variety of bioactive CaP species, such as hydroxyapatite (HA), amorphous CaP (ACP), octacalcium phosphate (OCP), and dicalcium phosphate dihydrate (DCPD). The compositions of the coatings during the nucleation and crystallization processes are tracked and analyzed using X-ray absorption near-edge structure (XANES). The variation of CaP species in the resulted coatings are found strongly dependent on the choice of metal substrates, which leads to different bioactivities. By comparing the proliferation and differentiation of osteoblast cells (MC3T3-E1) on the CaP coatings, correlations between CaP species and their bioactivities are established.

Automated polyvinylidene difluoride hollow fiber liquid-phase microextraction of flunitrazepam in plasma and urine samples for gas chromatography/tandem mass spectrometry.

A new polyvinylidene difluoride (PVDF) hollow fiber (200 microm wall thickness, 1.2mm internal diameter, 0.2 microm pore size) was compared with two other polypropylene (PP) hollow fibers (200, 300 microm wall thickness, 1.2mm internal diameter, 0.2 microm pore size) in the automated hollow fiber liquid-phase microextraction (HF-LPME) of flunitrazepam (FLNZ) in biological samples. With higher porosity and better solvent compatibility, the PVDF hollow fiber showed advantages with faster extraction efficiency and operational accuracy. Parameters of the CTC autosampler program for HF-LPME in plasma and urine samples were carefully investigated to ensure accuracy and reproducibility. Several parameters influencing the efficiency of HF-LPME of FLNZ in plasma and urine samples were optimized, including type of porous hollow fiber, organic solvent, agitation rate, extraction time, salt concentration, organic modifier, and pH. Under optimal conditions, extraction recoveries of FLNZ in plasma and urine samples were 6.5% and 83.5%, respectively, corresponding to the enrichment factor of 13 in plasma matrix and 167 in urine matrix. Excellent sample clean-up was observed and good linearities (r(2)=0.9979 for plasma sample and 0.9995 for urine sample) were obtained in the range of 0.1-1000 ng/mL (plasma sample) and 0.01-1000 ng/mL (urine sample). The limits of detection (S/N=3) were 0.025 ng/mL in plasma matrix and 0.001 ng/mL in urine matrix by gas chromatography/mass spectrometry/mass spectrometry.