Targeted Ferroptosis-Immunotherapy Synergy: Enhanced Antiglioma Efficacy with Hybrid Nanovesicles Comprising NK Cell-Derived Exosomes and RSL3-Loaded Liposomes.

Ferroptosis therapy and immunotherapy have been widely used in cancer treatment. However, nonselective induction of ferroptosis in tumors is prone to immunosuppression, limiting the therapeutic effect of ferroptosis cancer treatment. To address this issue, this study reports a customized hybrid nanovesicle composed of NK cell-derived extracellular versicles and RSL3-loaded liposomes (hNRVs), aiming to establish a positive cycle between ferroptosis therapy and immunotherapy. Thanks to the enhanced permeability and retention effect and the tumor homing characteristics of NK exosomes, our data indicate that hNRVs can actively accumulate in tumors and enhance cellular uptake. FASL, IFN-γ, and RSL3 are released into the tumor microenvironment, where FASL derived from NK cells effectively lyses tumor cells. RSL3 downregulates the expression of GPX4 in the tumor, leading to the accumulation of LPO and ROS, and promotes ferroptosis in tumor cells. The accumulation of IFN-γ and TNF-α stimulates the maturation of dendritic cells and effectively induces the inactivation of GPX4, promoting lipid peroxidation, making them sensitive to ferroptosis and indirectly promoting the occurrence of ferroptosis. This study highlights the role of the customized hNRV platform in enhancing the effectiveness of synergistic treatment with selective delivery of ferroptosis inducers and immune activation against glioma without causing additional side effects on healthy organs.

Oriented polyaniline/poly-l-lactic acid/gelatin nanofiber scaffolds promote outgrowth of spiral ganglion neurons.

Sensorineural hearing loss (SNHL) is caused by the loss of sensory hair cells (HCs) and/or connected spiral ganglion neurons (SGNs). The current clinical conventional treatment for SNHL is cochlear implantation (CI). The principle of CI is to bypass degenerated auditory HCs and directly electrically stimulate SGNs to restore hearing. However, the effectiveness of CI is limited when SGNs are severely damaged. In the present study, oriented nanofiber scaffolds were fabricated using electrospinning technology to mimic the SGN spatial microenvironment in the inner ear. Meanwhile, different proportions of polyaniline (PANI), poly-l-lactide (PLLA), gelatin (Gel) were composited to mimic the composition and mechanical properties of auditory basement membrane. The effects of oriented PANI/PLLA/Gel biomimetic nanofiber scaffolds for neurite outgrowth were analyzed. The results showed the SGNs grew in an orientation along the fiber direction, and the length of the protrusions increased significantly on PANI/PLLA/Gel scaffold groups. The 2% PANI/PLLA/Gel group showed best effects for promoting SGN adhesion and nerve fiber extension. In conclusion, the biomimetic oriented nanofiber scaffolds can simulate the microenvironment of SGNs as well as promote neurite outgrowth in vitro, which may provide a feasible research idea for SGN regeneration and even therapeutic treatments of SNHL in future.

Multifunctional TaCu-nanotubes coated titanium for enhanced bacteriostatic, angiogenic and osteogenic properties.

In this study, multifunctional tantalum copper composite nanotubes (TaCu-NTs) were coated on titanium for enhanced bacteriostatic, angiogenic and osteogenic properties. Three coatings of Ta, TaCu1 (Ta: Cu = 4:1 at.%), and TaCu2 (Ta: Cu = 1:1 at.%) were deposited on titanium by magnetron sputtering. The bare titanium and the three coatings were subsequently anodized into four kinds of nanotubes (NT) of TNT, Ta-NT, TaCu1-NT, and TaCu2-NT, respectively. The released copper ions measured by inductively coupled plasma atomic emission spectroscopy (ICP/AES) presented that TaCu2-NT coating released the highest amount of copper ions, which led to the best bacteriostasis against Escherichia coli and Staphylococcus aureus. Potentiodynamic polarization tests clarified that Ta-NT showed the highest corrosion resistance, followed by TaCu1-NT and TaCu2-NT. TaCu2-NT showed not only the best angiogenic property in terms of cell migration, tube formation, and real-time quantitative polymerase chain reaction (RT-qPCR) of human umbilical vein endothelial cells (HUVECs), but also the best osteogenic property in terms of cell viability, alkaline phosphatase activity, and mineralization of MC3T3-E1 cells. Therefore, TaCu2-NT coating has a greater potential than the other coatings of TNT, Ta-NT and TaCu1-NT in promoting bacteriostasis, angiogenesis and osteointegration for titanium implants.

Facile formation of salecan/agarose hydrogels with tunable structural properties for cell culture.

Salecan polysaccharide produced by Agrobacterium sp. ZX09 is an attractive biopolymer to construct hydrogel scaffolds for cell culture. However, some limitations such as poor mechanical performance, complicated fabrication process and slow gelation times still exist in the biomedical applications of microbial-based salecan polysaccharide hydrogels. Here, a series of polysaccharide hydrogels composed of salecan and agarose with adjustable structural properties are designed. The resultant hybrid salecan/agarose hydrogels exhibit controllable physical and chemical properties including thermal stability, water uptake, mechanical strength and microarchitecture, which can be readily realized with minimum change of the polysaccharide content. Furthermore, cytotoxicity assays reveal that the designed composite hydrogels are non-toxic. More importantly, these hydrogels support cell survival, proliferation, and migration. Together, this work opens up a new avenue to build polysaccharide hydrogel platforms for tissue engineering.