Materials science & engineering. C, Materials for biological applications最新文献

A sterically stabilized unilamellar nanocarrier vesicle (SSV) system containing dipalmitoylphosphatidylcholine, cholesterol, ursolic acid and PEGylated phospholipid has been developed by exploiting the structural advantages of ursolic acid: by spontaneously attaching to the lipid head groups, it induces curvature at the outer side of the bilayers, allowing the preparation of size-limited vesicles without extrusion. Ursolic acid (UA) also interacts with the PEG chains, supporting steric stabilization even when the amount of PEGylated phospholipid is reduced. Using fluorescence immunohistochemistry, vesicles containing ursolic acid (UA-SSVs) were found to accumulate in the tumor in 3 h on xenografted mouse, suggesting the potential use of these vesicles for passive tumor targeting.

Further on, mono- and combination therapy with UA and six different kinase inhibitors (crizotinib, erlotinib, foretinib, gefitinib, refametinib, trametinib) was tested on seven cancer cell-lines. In most combinations synergism was observed, in the case of trametinib even at very low concentration (0.001 μM), which targets the MAPK pathway most often activated in human cancers. The coupled intercalation of UA and trametinib (2:1 molar ratio) into vesicles causes further structural advantageous molecular interactions, promoting the formation of small vesicles. The high drug:lipid molar ratio (~0.5) in the novel type of co-delivery vesicles enables their direct medical application, possibly also overcoming the multidrug resistance effect.

Hydrogels have attracted much attention for biomedical and pharmaceutical applications due to the similarity of their biomimetic structure to the extracellular matrix of natural living tissues, tunable soft porous microarchitecture, superb biomechanical properties, proper biocompatibility, etc. Injectable hydrogels are an exciting type of hydrogels that can be easily injected into the target sites using needles or catheters in a minimally invasive manner. The more comfortable use, less pain, faster recovery period, lower costs, and fewer side effects make injectable hydrogels more attractive to both patients and clinicians in comparison to non-injectable hydrogels. However, it is difficult to achieve an ideal injectable hydrogel using just a single material (i.e., polymer). This challenge can be overcome by incorporating nanofillers into the polymeric matrix to engineer injectable nanocomposite hydrogels with combined or synergistic properties gained from the constituents. This work aims to critically review injectable nanocomposite hydrogels, their preparation methods, properties, functionalities, and versatile biomedical and pharmaceutical applications such as tissue engineering, drug delivery, and cancer labeling and therapy. The most common natural and synthetic polymers as matrices together with the most popular nanomaterials as reinforcements, including nanoceramics, carbon-based nanostructures, metallic nanomaterials, and various nanosized polymeric materials, are highlighted in this review.

Bacterial infections are the major challenges of wound treatment in current clinical applications. In this study, Three-dimensional (3D) antibacterial wound dressing has been fabricated via introducing N-halamine/TiO₂ to gelatin methacrylate and xanthan gum. The prepared 3D printed dressings showed ideal swelling ratio and excellent water uptake efficiency. TiO₂ nanoparticles were introduced by in-situ to improve the ultraviolet stability of N-halamines. The 3D printed GX2-TiO₂-PSPH-Cl prepared dressings containing titanium dioxide retained 0.19% active chlorine after ultraviolet irradiation for 20 min, which was much higher than that of N-halamine dressings without the addition of TiO₂. The 3D printed dressings showed good antibacterial activity, and 100% of Escherichia coli O157:H7 and Staphylococcus aureus were inactivated after 60 min of contact. Furthermore, the biofilm test indicated that the 3D antibacterial dressings were able to inhibit the formation of bacterial biofilm. The 3D printed dressings possess outstanding biocompatibility. Moreover, in vivo data demonstrated that the 3D printed dressings could significantly accelerate wound healing in a mouse model, indicating that the developed 3D printed dressings are ideal candidates for wound treatment.

Chemodynamic therapy (CDT) involving the highly toxic hydroxyl radical (OH) has exhibited tremendous potentiality in combating bacterial infection. However, its antibacterial efficacy is still unsatisfactory due to the insufficient H₂O₂ levels and near neutral pH at infection site. Herein, a glucose-fueled and H₂O₂-self-supplying OH nanogenerator (pFe₃O₄@GOx) based on cascade catalytic reactions is developed by immobilizing glucose oxidase (GOx) on the surface of PAA-coated Fe₃O₄ (pFe₃O₄). Magnetic pFe₃O₄ can act as a horseradish peroxidase-like nanozyme, catalyzing the decomposition of H₂O₂ into OH under acidic conditions for CDT. The immobilized GOx can continuously convert non-toxic glucose into gluconic acid and H₂O₂, and the former improves the catalytic activity of pFe₃O₄ nanozymes by decreasing pH value. The self-supplying H₂O₂ molecules effectively enhance the OH generation, resulting in the high antibacterial efficacy. In vitro studies demonstrate that the pFe₃O₄@GOx conducts well in reducing pH value and improving H₂O₂ level for self-enhanced CDT. Moreover, the cascade catalytic reaction of pFe₃O₄ and GOx effectively avoids strong toxicity caused by directly adding high concentrations of H₂O₂ for CDT. It is worth mentioning that the pFe₃O₄@GOx performs highly efficient in vivo CDT of bacteria-infected wound via the localized long-term magnetic retention at infection site and causes minimal toxicity to normal tissues at therapeutic doses. Therefore, the developed glucose-fueled OH nanogenerators are a potential nano-antibacterial agent for the treatment of wound infections.

MnO₂ owns distinct redox, imaging, and degradable properties corresponding to the tumor microenvironment. However, the onefold structure and non-modifiable property cause many obstacles to anticancer applications. In this report, we first prepared a typical core-shell gold nanorod (GNR)/manganese dioxide (MnO₂) nanoparticles (GNR/MnO₂ NPs). Interestingly, the MnO₂ had a mesoporous channel and modifiable hydroxyl group (OH). Here, the unique ‘OH’ groups were modified and further grafted with poly(N-isopropylacrylamide-co-acrylic acid) (PNA). As a dual-sensitive hydrogel, it was selected as the thermal/pH-sensitive component in the hybrid nanoparticles (GNR/MnO₂/PNA NPs). The anticancer drug doxorubicin hydrochloride (DOX) was selected and loaded into the hybrid nanoparticles (GNR/MnO₂/PNA-DOX NPs). The GNR/MnO₂/PNA NPs achieved satisfying drug-loading efficiency and glutathione (GSH)/pH/thermal-responsive drug-controlled release. As a side benefit, the GNR/MnO₂/PNA NPs showed potential as excellent near-infrared (NIR)-excited nanoplatforms for photothermal therapy (PTT). Delightedly, the studies demonstrated that the GNR/MnO₂/PNA-DOX NPs showed a noticeable killing effect on tumor cells, whether it is tumor cell-triggered drug release or photothermal effect. Besides, it not only could enhance mitochondrial damage but also could inhibit the migration and invasion of tumor cells. Quite the reverse, it had little negative impact on normal cells. The feature can prevent anticancer drugs and nanoparticles from killing normal cells. Consequently, GNR/MnO₂/PNA NPs have potential applications in drug delivery and synergistic therapy due to these advantageous features.