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

The administration and controlled release of drugs over time remains one of the greatest challenges of science today. In the nanomaterials field, anisotropic gold nanoparticles (AuNPs) with plasmon bands centered at the near-infrared region (NIR), such as gold nanorods (AuNRs) and gold nanoprisms (AuNPrs), under laser irradiation, locally increase the temperature, allowing the release of drugs. In this sense, temporally controlled drug delivery could be promoted by external stimuli using thermo-reversible chemical reactions, such as Diels-Alder cycloadditions from a diene and a dienophile fragment (compound a). In this study, an antitumor drug (methotrexate, MTX) was linked to plasmonic AuNPs by a Diels-Alder adduct (compound c), which after NIR suffers a retro-Diels-Alder reaction, producing release of the drug (compound b). We obtained two nanosystems based on AuNRs and AuNPrs. Both nanoconstructs were coated with BSA-r₈ (Bovine Serum Albumin functionalized with Arg₈, all-D octa arginine) in order to increase the colloidal stability and promote internalization of the nanosystems on HeLa and SK-BR-3 cells. In addition, the presence of BSA allows protecting the cargo from being released on the extracellular environment and promotes the photothermal release of the drug in the presence of glutathione (GSH). The nanosystems' drug release profile was evaluated after NIR irradiation in the presence and absence of glutathione (GSH), showing a considerable increase of drug release when NIR light and glutathione were combined. This work broadens the range of possibilities of using two complementary strategies for the controlled release of an antitumor drug from AuNRs and AuNPrs: the photothermal cleavage of a thermolabile adduct controlled by an external stimulus (laser irradiation), complemented with the use of the intracellular metabolite GSH.

Cellular defense system represented by glutathione (GSH) greatly weakens the outcomes of cancer therapy by antioxidation and detoxification. GSH depletion has been proved to be an effective way to enhance the efficacy of reactive oxygen species (ROS)-based therapies and chemotherapy. However, the existing strategies of GSH depletion still face the problems of unclear biosafety and high complexity of multicomponent co-delivery. In this study, we developed a GSH-depleting carrier platform based on disulfide-bridged mesoporous organosilica nanoparticles (MONs) to destroy the cellular defense system for cancer therapy. Responding to the high level of GSH in cancer cells, the disulfide bonds in the framework of MONs could be broken and consumed substantial GSH at the same time. Moreover, this process also promoted the degradation of MONs. In order to evaluate the effect of this platform in cancer therapy, chemotherapeutic drug cisplatin was loaded into MONs (Pt@MONs) to treat drug-resistant non-small cell lung cancer. In vitro and in vivo results indicated that Pt@MONs efficiently triggered GSH depletion, promoted platinum-DNA adduct formation, and induced cell apoptosis, resulting in significant tumor growth inhibition without marked toxicity. Taken together, the cellular defense system-destroying nanoparticles provide a promising platform for enhanced cancer therapy.

Plasma-based strategies offer several advantages for developing antibacterial biomaterials and can be used directly or combined with other surface modification techniques. Direct plasma strategies can be classified as plasma surface modifications that derive antibacterial property by tailoring surface topography or surface chemistry. Nano patterns induced by plasma modification can exhibit antibacterial property and promote the adhesion and proliferation of mammalian cells, creating antibacterial and biocompatible surfaces. Antibacterial effect by tailoring surface chemistry via plasma can be attained by either creating bacteriostatic surfaces or bactericidal surfaces. Plasma-assisted strategies incorporate plasma processes in combination with other surface modification techniques. Plasma coating can serve as a drug-eluting reservoir and diffusion barrier. The plasma-functionalized surface can serve as a platform for grafting antibacterial agents, and plasma surface activation can improve the adhesion of polymeric layers with antibacterial properties. This article critically reviews plasma-based strategies reported in the recent literature for the development of antibacterial biomaterial surfaces. Studies using both atmospheric and low-pressure plasmas are included in this review. The findings are discussed in terms of the trends in material and precursor selection, modification stability, antibacterial efficacy, the choice of bacterial strains tested, cell culture findings, critical aspects of in vitro performance testing and in vivo experimental design.

In this study, modular two-in-one nano-cocktails were synthesised to provide treatment of inflammatory diseases and also enable tracking of their delivery to the disease sites. Chitosan nano-cocktails loaded with treatment module (cerium oxide nanoparticles) and imaging module (iron oxide nanoparticles) were synthesised by electrostatic self-assembly (Chit-IOCO) and ionic gelation method (Chit-TPP-IOCO), respectively. Their MRI capability, anti-inflammatory and anti-fibrosis ability were investigated. Results demonstrated that Chit-IOCO significantly reduced the expression of TNF-α and COX-2, while Chit-TPP-IOCO reduced IL-6 in the LPS-stimulated macrophages RAW264.7. Cytotoxicity studies showed that the nano-cocktails inhibited the proliferation of macrophages. Additionally, Chit-IOCO exhibited higher in vitro MRI relaxivity than Chit-TPP-IOCO, indicating that Chit-IOCO is a better MRI contrast agent in macrophages. It was possible to track the delivery of Chit-IOCO to the inflamed livers of CCl₄-treated C57BL/6 mice, demonstrated by a shortened T₂^⁎ relaxation time of the livers after injecting Chit-IOCO into mice. In vivo anti-inflammatory and blood tests demonstrated that Chit-IOCO reduced inflammation-related proteins (TNF-a, iNOS and Cox-2) and bilirubin in CCl₄ treated C57BL/6. Histology images indicated that the nano-cocktails at the treatment doses did not affect the organs of the mice. Importantly, the nano-cocktail reduced fibrosis of CCl₄-treated mouse liver. This is the first reported data on the anti-inflammation and anti-fibrosis efficacy of Chit-IOCO in C57BL/6 mouse liver inflammation model. Overall, Chit-IOCO nanoparticles have shown great potential in MR imaging/detecting and treating/therapeutic capabilities for inflammatory diseases.

Quercetin (Que) has been proved to have various biological activities, including anti-oxidation, anti-inflammation and anti-virus, showing great potential in liver protection. However, its water insolubility leads to low bioavailability. Therefore, the development of a suitable drug delivery fashion is imminent. In recent years, liposomes have been widely used in the fields of drug delivery and gene transfer thanks to the cell membrane like structure, easy surface-modification and high encapsulation efficiency. Herein, we fabricated Que loaded anionic liposomes. Galactosylated chitosan (GC) was simply attached to the surfaces of liposomes through electrostatic adsorption to achieve targeted delivery by binding to asialoglycoprotein receptor (ASGPR). The results showed that Que loaded liposomes modified with GC (GC-Que-Lipo) could enrich the liver in mice through tail vein injection. Liposomes could achieve sustained drug release and GC-Que-Lipo promoted M2 polarization of macrophages. More importantly, it could maintain low content of AST, ALT, ALP and high level of GSH while reducing lipid oxidation, thereby protecting the liver from damage in acute liver injury model. In general, we expect to be able to acquire targeted and efficient delivery of quercetin through a facile approach, thus fulfill the prevention and treatment of liver diseases.

Inorganic/organic hybrids and bioactive glasses demonstrate promising potential as bone substitute biomaterials. A sol-gel hybrid consisting of silica bioactive glass and biodegradable polymer can combine the high bioactivity of a glass with the toughness of a polymer. In this study, multifunctional hybrids with a combination of organic-inorganic hybrid structure class II consisting of polyethyleneimine (PEI) generation 4 (G4) and bioactive glass with enhanced mechanical properties, mineralization, antibacterial, and osteogenesis activities were synthesized by the sol-gel method. Glycidoxypropyl) trimethoxysilane (GPTMS) with different concentrations was used as a covalent bonding agent between PEI polymer and bioactive glass. The effect of GPTMS content was assessed in the presence and absence of calcium in the hybrid structures in terms of morphology, wettability, mechanical properties, antibacterial activity, cell viability, and in vitro osteogenic differentiation properties. By increasing the amount of GPTMS, the compressive strength increased from 1.95 MPa to 2.34 MPa, which was comparable to human trabecular bone. All the hybrids presented antibacterial activity against Staphylococcus aureus, forming an inhibition zone of 13–16 mm. An increase in cell viability of 82.22% in PSCaG90 was obtained after 1 day of MG-63 cell culture. Alkaline phosphatase expression and mineralization of MG-63 cells increased in the PSCaG90 hybrid in the absence of an osteogenic medium compared to PSG60 and PSG90. The PSCaG90 hybrid indicated considerable in vitro osteogenic capacity in the absence of a differentiation medium, expressing high levels of bone-specific proteins including collagen I (COL1A1), Runt-related transcription factor 2 (RUNX2), osteopontin (OPN), and osteocalcin (OCN), compared to calcium-free hybrids. Overall, our results suggest that the presence of calcium in the PSCaG90 leads to a significant increase in osteogenic differentiation of MG-63 cells even in the absence of differentiation medium, which suggests these hybrid structures with multifunctional properties as promising candidates for bone repair.

Implanted biomaterials can be regarded in a cornerstone in the domain of bone surgery. Their surfaces are expected to fulfil two particular requirements: preventing the settlement and the development of bacteria, and stimulating bone cells in view to foster osseointegration. Therefore, a modern approach consists in the design of dual functional coatings with both antibacterial and osteogenic features. To this end, we developed ultrathin Layer-by-Layer (LbL) coatings composed of biocompatible polyelectrolytes, namely chondroitin sulfate A (CSA) and poly-l-lysine (PLL). The coatings were crosslinked with genipin (GnP), a natural and biocompatible crosslinking agent, to increase their resistance against environmental changes, and to confer them adequate mechanical properties with regards to bone cell behaviors. Antibacterial activity was obtained with nisin Z, an antimicrobial peptide (AMP), which is active against gram-positive bacteria. The coatings had a significant bactericidal impact upon Staphylococcus aureus, with fully maintained bone cell adhesion, proliferation and osteogenic differentiation.

Early osteointegration is essential for biomedical implants. Surface modifications can significantly compensate for an implant's lack of biocompatibility and osteo-differentiation. They can also be designed to promote angiogenesis in order to assist osteogenesis and ultimately facilitate bone regeneration. In this study, a polydopamine-assisted strontium-substituted apatite coating (Ti@PDA + SrHA) was fabricated on a multifunctional titanium implant to induce both angiogenic and osteogenic abilities for rapid osseointegration. Polydopamine and Sr-substituted hydroxyapatite were coated on the implant through biomineralization. The in vitro results showed that Ti@PDA + SrHA improved cell adhesion and increased the proliferation of rat bone marrow-derived mesenchymal stem cells (rBMSCs) and human umbilical vein endothelial cells (HUVECs). Ti@PDA + SrHA upregulated the expression of ALP activity and osteogenic genes in rBMSCs and elevated angiogenic genes in both rBMSCs and HUVECs. Mechanically, the FAK/MAPK signaling pathway was activated in rBMSCs, and the PI3K/AKT signaling pathway was activated in both rBMSCs and HUVECs. Consistent with these findings, Ti@PDA + SrHA accelerated new bone formation and rapid osseointegration in the femoral condyle implantation study with good stability. Overall, we fabricated a multifunctional biocompatible implant with better angiogenic and osteogenic performance compared to the non-coated implant.

Fast disintegrating and dissolving nanofiber (NF) mat was devised to deliver roxithromycin for the treatment of the respiratory tract infection. NF membrane was made by an electrospinning process with poly(vinyl alcohol) (PVA), hydroxypropyl-β-cyclodextrin (HP-β-CD), and d-α-tocopheryl polyethylene glycol succinate (TPGS) for local application of roxithromycin. Roxithromycin has a poor water solubility thus HP-β-CD is introduced for enhancing drug solubility by forming an inclusion complex in this study. The addition of TPGS provided multiple roles such as accelerating wetting, disintegration, and dissolution speed and overcoming bacterial resistance. Roxithromycin was successfully entrapped in NF structure and drug amorphization occurred during the electrospinning process. PVA/HP-β-CD/TPGS/roxithromycin (PHTR) NF exhibited faster wetting, disintegration, and dissolution speed rather than the other NF mats. PHTR NF displayed higher antibacterial potentials in Gram-negative bacteria (E. coli) and Gram-positive bacteria (S. aureus) compared to other NF mat formulations. The administration of PHTR NF to oral cavity in pneumococcal disease mouse model provided the most efficient therapeutic potentials in lung tissue. Designed multiple phase-based NF mat may be one of powerful local drug delivery systems for the therapy of respiratory tract infection.