OBJECTIVE: Cancer remains a significant global health challenge, necessitating the development of effective treatment approaches. Developing synergistic therapy can provide a highly promising strategy for anti-cancer treatment through combining the benefits of various mechanisms. METHODS: In this study, we developed a synergistic strategy for chemo-photothermal therapy by constructing nanocomposites using gold nanorods (GNRs) and tetrahedral framework nucleic acids (tFNA) loaded with the anti-tumor drug doxorubicin (DOX). RESULTS: Our in vitro studies have systematically clarified the anti-cancer behaviors of tFNA-DOX@GNR nanocomposites, characterized by their enhanced cellular uptake and proficient lysosomal escape capabilities. It was found that the key role of tFNA-DOX@GNR nanocomposites in tumor ablation is primarily due to their capacity to induce cytotoxicity in tumor cells via a photothermal effect, which generates instantaneous high temperatures. This mechanism introduces various responses in tumor cells, facilitated by the thermal effect and the integrated chemotherapeutic action of DOX. These reactions include the induction of endoplasmic reticulum stress, characterized by elevated reactive oxygen species levels, the promotion of apoptotic cell death, and the suppression of tumor cell proliferation. CONCLUSION This work exhibits the potential of synergistic therapy utilizing nanocomposites for cancer treatment and offers a promising avenue for future therapeutic strategies.
Doxorubicin/chemistry* ; Gold/chemistry* ; Nanotubes/chemistry* ; Humans ; Nanocomposites/chemistry* ; Cell Line, Tumor ; Nucleic Acids/chemistry* ; Antibiotics, Antineoplastic/pharmacology* ; Antineoplastic Agents/administration & dosage*

This study was to develop a new method for detecting circulating tumor cells (CTCs) with high sensitivity and specificity, therefore to detect the colorectal cancer as early as possible for improving the detection rate of the disease. To this end, we prepared some micro-column structure microchips modified with graphite oxide-streptavidin (GO-SA) on the surface of microchips, further coupled with a broad-spectrum primary antibody (antibody1, Ab₁), anti-epithelial cell adhesion molecule (anti-EpCAM) monoclonal antibody to capture CTCs. Besides, carboxylated multi-walled carbon nanotubes (MWCNTs-COOH) were coupled with colorectal cancer related antibody as specific antibody 2 (Ab₂) to prepare complex. The sandwich structure consisting of Ab₁-CTCs-Ab₂ was constructed by the microchip for capturing CTCs. And the electrochemical workstation was used to detect and verify its high sensitivity and specificity. Results showed that the combination of immunosensor and micro-nano technology has greatly improved the detection sensitivity and specificity of the immunosensor. And we also verified the feasibility of the immunosensor for clinical blood sample detection, and successfully recognitized detection and quantization of CTCs in peripheral blood of colorectal cancer patients by this immunosensor. In conclusion, the super sandwich immunosensor based on micro-nano technology provides a new way for the detection of CTCs, which has potential application value in clinical diagnosis and real-time monitoring of disease.
Humans ; Nanotubes, Carbon/chemistry* ; Neoplastic Cells, Circulating/pathology* ; Biosensing Techniques ; Immunoassay/methods* ; Antibodies ; Colorectal Neoplasms/diagnosis* ; Electrochemical Techniques/methods* ; Gold/chemistry*

Tunneling nanotube (TNT) is a newly discovered communication mode between animal cells in recent years, which have important physiological and pathological significance. However, the role of TNT in bone biology is still unclear. At present, there are many reports about tunneling nanotubes in bone marrow mesenchymal stem cells, osteoclast precursor cells, osteoblasts and immune cells. This review describes the research advances of TNT and its research progress in bone biology. It looks forward to the research direction of TNT in oral and maxillofacial bone development and bone biology, to provide new strategies for the maintenance of bone homeostasis and the treatment of bone diseases.
Animals ; Bone and Bones ; Nanotubes ; Osteoclasts ; Biology ; Cell Communication/physiology*

Objective: To fabricate TiO₂ nanotube material functionalized by antimicrobial peptide LL-37, and to explore its effects on biological behaviors such as adhesion and migration of human keratinocytes (HaCaT) and its antibacterial properties. Methods: The TiO₂ nanotube array (NT) was constructed on the surface of polished titanium (PT) by anodization, and the antimicrobial peptide LL-37 was loaded on the surface of TiO₂ nanotube (LL-37/NT) by physical adsorption. Three samples were selected by simple random sampling in each group. Surface morphology, roughness, hydrophilicity and release characteristics of LL-37 of the samples were analyzed with a field emission scanning electron microscope, an atomic force microscope, a contact angle measuring device and a microplate absorbance reader. HaCaT cells were respectively cultured on the surface of three groups of titanium samples. Each group had 3 replicates. The morphology of cell was observed by field emission scanning electron microscope. The number of cell adhesion was observed by cellular immunofluorescence staining. Cell counting kit-8 (CCK-8) assay was used to detect cell proliferation. Wound scratch assay was used to observe the migration of HaCaT. The above experiments were used to evaluate the effect of each group on the biological behavior of HaCaT cells. To evaluate their antibacterial effects, Porphyromonas gingivalis (Pg) was respectively inoculated on the surface of three groups of titanium samples. Each group had 3 replicates. The morphology of bacteria was observed by field emission scanning electron microscope. Bacterial viability was determined by live/dead bacterial staining. Results: A uniform array of nanotubes could be seen on the surface of titanium samples in LL-37/NT group, and the top of the tube was covered with granular LL-37. Compared with PT group [the roughness was (2.30±0.18) nm, the contact angle was 71.8°±1.7°], the roughness [(20.40±3.10) and (19.10±4.11) nm] and hydrophilicity (the contact angles were 22.4°±3.1° and 25.3°±2.2°, respectively) of titanium samples increased in NT and LL-37/NT group (P<0.001). The results of in vitro release test showed that the release of antimicrobial peptide LL-37 was characterized by early sudden release (1-4 h) and long-term (1-7 d) slow release. With the immunofluorescence, more cell attachment was found on NT and LL-37/NT than that on PT at the first 0.5 and 2.0 h of culture (P<0.05). The results of CCK-8 showed that there was no significant difference in the proliferation of cells among groups at 1, 3 and 5 days after culture. Wound scratch assay showed that compared with PT and NT group, the cell moved fastest on the surface of titanium samples in LL-37/NT group at 24 h of culture [(96.4±4.9)%] (F=35.55, P<0.001). A monolayer cells could be formed and filled with the scratch in 24 h at LL-37/NT group. The results of bacterial test in vitro showed that compared with the PT group, the bacterial morphology in the NT and LL-37/NT groups was significantly wrinkled, and obvious bacterial rupture could be seen on the surface of titanium samples in LL-37/NT group. The results of bacteria staining showed that the green fluorescence intensity of titanium samples in LL-37/NT group was the lowest in all groups (F=66.54,P<0.001). Conclusions: LL-37/NT is beneficial to the adhesion and migration of HaCaT cells and has excellent antibacterial properties, this provides a new strategy for the optimal design of implant neck materials.
Humans ; Titanium/chemistry* ; Antimicrobial Peptides ; Cathelicidins ; Sincalide ; Anti-Bacterial Agents/pharmacology* ; Nanotubes/chemistry* ; Dental Materials ; Bacteria ; Keratinocytes ; Surface Properties

Carbon nanotube (CNT) composite materials are very attractive for use in neural tissue engineering and biosensor coatings. CNT scaffolds are excellent mimics of extracellular matrix due to their hydrophilicity, viscosity, and biocompatibility. CNTs can also impart conductivity to other insulating materials, improve mechanical stability, guide neuronal cell behavior, and trigger axon regeneration. The performance of chitosan (CS)/polyethylene glycol (PEG) composite scaffolds could be optimized by introducing multi-walled CNTs (MWCNTs). CS/PEG/CNT composite scaffolds with CNT content of 1%, 3%, and 5% (1%=0.01 g/mL) were prepared by freeze-drying. Their physical and chemical properties and biocompatibility were evaluated. Scanning electron microscopy (SEM) showed that the composite scaffolds had a highly connected porous structure. Transmission electron microscope (TEM) and Raman spectroscopy proved that the CNTs were well dispersed in the CS/PEG matrix and combined with the CS/PEG nanofiber bundles. MWCNTs enhanced the elastic modulus of the scaffold. The porosity of the scaffolds ranged from 83% to 96%. They reached a stable water swelling state within 24 h, and swelling decreased with increasing MWCNT concentration. The electrical conductivity and cell adhesion rate of the scaffolds increased with increasing MWCNT content. Immunofluorescence showed that rat pheochromocytoma (PC12) cells grown in the scaffolds had characteristics similar to nerve cells. We measured changes in the expression of nerve cell markers by quantitative real-time polymerase chain reaction (qRT-PCR), and found that PC12 cells cultured in the scaffolds expressed growth-associated protein 43 (GAP43), nerve growth factor receptor (NGFR), and class III β‍-tubulin (TUBB3) proteins. Preliminary research showed that the prepared CS/PEG/CNT scaffold has good biocompatibility and can be further applied to neural tissue engineering research.
Animals ; Axons ; Biocompatible Materials/chemistry* ; Chitosan/chemistry* ; Nanotubes, Carbon/chemistry* ; Nerve Regeneration ; Polyethylene Glycols ; Porosity ; Rats ; Tissue Engineering/methods* ; Tissue Scaffolds/chemistry*

OBJECTIVE: To investigate the effects of multi-walled carbon nanotubes (MWCNTs) with different length or chemical modification on endothelial cell activation and to explore the role of nucleotide-binding oligomerization domain-like receptor family pyrin domain containing 3 (NLRP3) inflammasome. METHODS: MWCNTs were characterized by dynamic light scattering (DLS) after being suspended in culture medium. The immortalized mouse cerebral microvascular endothelial cell line b.End3 was treated with short MWCNTs (S-MWCNT, 0.5 to 2 μm), long MWCNTs (L-MWCNT, 10 to 30 μm) and the above long MWCNTs functionalized by carboxyl-(L-MWCNT-COOH), amino-(L-MWCNT-NH₂) or hydroxyl-(L-MWCNT-OH) modification. Cytotoxicity of MWCNTs in b.End3 cells was determined by cell counting kit-8 (CCK-8) assay and lactate dehydrogenase (LDH) release assay, and non-toxic low dose was selected for subsequent experiments. Effects of all types of MWCNTs on the endothelial activation of b.End3 were determined by the measurement of vascular cell adhesion molecule-1 (VCAM-1) concentration in cell supernatant and adhesion assay of human monocytic cell line THP-1 to b.End3.To further elucidate the mechanism involved, the protein expressions of nucleotide-binding oligomerization domain-like receptor family pyrin domain containing 3(NLRP3) in cells treated with S-MWCNT, L-MWCNT and L-MWCNT-COOH were measured by Western blot. RESULTS: At a higher concentration (125 μg/cm²) and treated for 24 h, all types of MWCNTs significantly inhibited viability of b.End3 cells. At a sub-toxic concentration (6.25 μg/cm²), all types of MWCNTs treated for 12 h significantly induced the activation of b.End3 cells, as evidenced by the elevated VCAM-1 release and THP-1 adhesion. Compared with S-MWCNT, L-MWCNT significantly promoted endothelial cell activation. L-MWCNT and L-MWCNT-COOH activated b.End3 cells to a similar extent. Furthermore, treatment with S-MWCNT, L-MWCNT and L-MWCNT-COOH increased NLRP3 expression in a time-dependent manner at 6.25 μg/cm². Compared with S-MWCNT, cells treated with L-MWCNT for 4 h and 12 h exhibited significantly increased protein expressions of NLRP3. However, no significant differences were detected in the level of NLRP3 protein in cells treated with L-MWCNT and L-MWCNT-COOH. CONCLUSION Compared with the surface chemical modification, length changes of MWCNTs exerted more influence on endothelial cell activation, which may be related to the activation of NLRP3 inflammasome. Our study contributes further understanding of the impact of MWCNTs on endothelial cells, which may have implications for the improvement of safety evaluation of MWCNTs.
Cell Line ; Cell Survival ; Endothelial Cells ; Nanotubes, Carbon/toxicity* ; Vascular Cell Adhesion Molecule-1

The aim of this study was to evaluate the biological efficacy of a unique perpendicular protrusion of type-I collagen (Col-I) from TiO
Animals ; Cell Adhesion ; Collagen Type I ; Mice ; NIH 3T3 Cells ; Nanotubes ; Surface Properties ; Titanium

The aim of this study was to examine the bioactivity and osseointegration of Ti-6Al-4V alloy implant which was modified by an anodic oxidation and a cyclic precalcification treatments. After blasting treatment using HAp (Hydroxyapatitie; HAp) powder which is resorbable blasting media (RBM) on the surface of Ti-6Al-4V alloy implants, the anodic oxidation treatment and the cyclic precalcification treatment were conducted to form nanotube TiO2 layer and HAp precipitation respectively. The surface morphology of the surface-treated Ti-6Al-4V alloy implant was investigated after immersion in the simulated body fluid(SBF) for 3 days to investigate the bioactivity. To investigate the effect of surface treatment on bonding between the implant and bone, RBM treated implant and RBM-anodization-cyclic precalcification(RACP) treated implant were placed on the distal side of both tibia diaphysis of rats, and then the removal torque of the implant was measured after 4 weeks. On the surface of RACP treated group, bone-like apatite precipitation was observed after immersion in SBF for 3 days. The removal torque was significantly higher in the RACP treated group than in the RBM treated group. The interfacial fracture between the implant and the new bone was observed in the RBM treated group, but both the cohesive fracture at the new bone and the interfacial fractures between the implant and the new bone were observed in the RACP treated group.
Alloys ; Animals ; Diaphyses ; Immersion ; Nanotubes ; Osseointegration ; Rats ; Tibia ; Torque

Electrodes ; Enterovirus A, Human ; isolation & purification ; Gold ; Metal Nanoparticles ; Nanotubes, Carbon

Cell-to-cell connections provide conduits for signal exchanges, and play important functional roles in physiological and pathological processes of multicellular organisms. Membrane nanotubes are common long-distance connections between cells, not only transfer molecule signals and mitochondria, but also cooperate with gap junction and other cell-to-cell communications to transfer signals. During the last decade, there are many studies about membrane nanotubes, which focus on the similarities and differences between membrane nanotubes and other cell-to-cell communications, as well as their biological functions. In the present review, we summarized the latest findings about the structural diversity, the similarities and differences in signal transmission with other types of cell-to-cell communications, and physiological and pathological roles of membrane nanotubes.
Cell Communication ; Cell Membrane ; physiology ; Gap Junctions ; physiology ; Humans ; Mitochondria ; physiology ; Nanotubes