Novel theranostics based on photosensitizer‐conjugated carbon dots is reported. The prepared C‐dots–Ce6 has good stability and high water dispersibility and solubility, non‐cytotoxicity, good ...biocompatibility, enhanced photosensitizer fluorescence detection and remarkable photodynamic efficacy upon irradiation. The C‐dots–Ce6 conjugate is a good candidate with excellent imaging and tumor‐homing ability for NIR fluorescence imaging monitored PDT treatment.
Photodynamic therapy (PDT) has emerged as an alternative and promising noninvasive treatment for cancer as well as non-cancer diseases, which involves the uptake of photosensitizers (PSs) by cancer ...cells followed by irradiation. The use of nanomaterials as carriers of PSs is a very promising approach to improve the development of PDT in clinical medicine. In this study, a novel folic acid-conjugated graphene oxide (GO) was strategically designed and prepared as targeting drug delivery system to achieve higher specificity. The second generation photosensitizer (PS) Chlorin e6 (Ce6) was effectively loaded into the system via hydrophobic interactions and π-π stacking. The nanocarriers can significantly increase the accumulation of Ce6 in tumor cells and lead to a remarkable photodynamic efficacy on MGC803 cells upon irradiation. These suggested that folic acid-conjugated GO loaded Ce6 had great potential as effective drug delivery system in targeting PDT.
•Instead of simply using scaffolds or following the tradition principle of large bone defects treatment, we proposed a novel concept: bone regenerative microenvironment (BRM). Through the regulation ...of three key entities of microenvironment: physical cues, chemical cues and biological cues, a favourable BRM can be achieved and thereby repair large bone defects.•This review not only concludes the scaffolds concerning the regulation of physical, chemical and biological cues in large physiological bone defects, but proposes the requirements of scaffolds when applied in large pathological bone defects.•In addition, for future study, we also put forward several perspectives, especially the study of high adhesive hydrogel, which warrant further development.
Bone is a complex biological tissue with a complicated hierarchical nanocomposite structure. The native microenvironment of the bone tissue may be significantly disrupted by large physiological and pathological bone defects. Bone defects are often treated via complex surgical procedures that involve the application of autografts or allografts. While these grafting procedures often suffer from insufficient natural bone stock and immunorejection. Moreover, these traditional treatment methods fail to simulate a regenerative microenvironment, which plays a significant role in regeneration of bone tissue and repair of large bone defects. To this end, various biomimetic scaffolds have been devised to mimic the native microenvironment of bone and thereby to simultaneously repair bone defects and promote bone regeneration. We propose here a novel concept, in vivo bone regenerative microenvironment (BRM), which enables repair of large bone defects and enhances new bone tissue formation with external regulation. In this review, we mainly focus on materials and methods for fabrication of biomimetic scaffolds, as well as their therapeutic efficacy in modulating the BRM of large physiological and pathological bone defects.
The scaffold‐free cell‐sheet technique plays a significant role in stem‐cell‐based regeneration. Furthermore, growth factors are known to direct stem cell differentiation and enhance tissue ...regeneration. However, the absence of an effective means to incorporate growth factors into the cell sheets hinders further optimization of the regeneration efficiency. Here, a novel design of magnetically controlled “growth‐factor‐immobilized cell sheets” is reported. A new Fe3O4 magnetic nanoparticle (MNP) coated with nanoscale graphene oxide (nGO@Fe3O4) is developed to label stem cells and deliver growth factors. First, the nGO@Fe3O4 MNPs can be easily swallowed by dental‐pulp stem cells (DPSCs) and have no influence on cell viability. Thus, the MNP‐labeled cells can be organized via magnetic force to form multilayered cell sheets in different patterns. Second, compared to traditional Fe3O4 nanoparticles, the graphene oxide coating provides plenty of carboxyl groups to bind and deliver growth factors. Therefore, with these nGO@Fe3O4 MNPs, bone‐morphogenetic‐protein‐2 (BMP2) is successfully incorporated into the DPSCs sheets to induce more bone formation. Furthermore, an integrated osteochondral complex is also constructed using a combination of DPSCs/TGFβ3 and DPSCs/BMP2. All these results demonstrate that the new cell‐sheet tissue‐engineering approach exhibits promising potential for future use in regenerative medicine.
A novel design for “growth‐factor‐immobilized cell sheets” formed under the control of magnetic force is introduced to optimize regeneration efficiency, based on a new nanoscale graphene‐oxide‐coated Fe3O4 magnetic nanoparticle. The nanocomposites provide a novel magnetically controlled vehicle for delivery of both stem cells and growth factors, and they exhibit promising potential for future use in regenerative medicine.
Colorectal cancer (CRC) development has been associated with increased proportions of Bacteroides fragilis and certain Streptococcus, Fusobacterium, and Peptostreptococcus species in the intestinal ...microbiota. We investigated associations between bacteremia from specific intestinal microbes and occurrence of CRC.
We performed a retrospective study after collecting data on 13,096 adult patients (exposed group) in Hong Kong hospitalized with bacteremia (identified by blood culture test) without a previous diagnosis of cancer from January 1, 2006 through December 31, 2015. We collected data on intestinal microbes previously associated with CRC (genera Bacteroides, Clostridium, Filifactor, Fusobacterium, Gemella, Granulicatella, Parvimonas, Peptostreptococcus, Prevotella, Solobacterium, and Streptococcus). Clinical information, including patient demographics, comorbid medical conditions, date of bacteremia, and bacterial species identified, were collected. The incidence of biopsy-proved CRC was compared between the exposed and unexposed (patients without bacteremia matched for age, sex, and comorbidities) groups.
The risk of CRC was increased in patients with bacteremia from B fragilis (hazard ratio HR = 3.85, 95% CI = 2.62–5.64, P = 5.5 × 10−12) or Streptococcus gallolyticus (HR = 5.73, 95% CI = 2.18–15.1, P = 4.1 × 10−4) compared with the unexposed group. In addition, the risk of CRC was increased in patients with bacteremia from Fusobacterium nucleatum (HR = 6.89, 95% CI = 1.70–27.9, P = .007), Peptostreptococcus species (HR = 3.06, 95% CI = 1.47–6.35, P = .003), Clostridium septicum (HR = 17.1, 95% CI = 1.82–160, P = .013), Clostridium perfringens (HR = 2.29, 95% CI = 1.16–4.52, P = .017), or Gemella morbillorum (HR = 15.2, 95% CI = 1.54–150, P = .020). We observed no increased risk in patients with bacteremia caused by microbes not previously associated with colorectal neoplasms.
In a retrospective analysis of patients hospitalized for bacteremia, we associated later diagnosis of CRC with B fragilis and S gallolyticus and other intestinal microbes. These bacteria might have entered the bloodstream from intestinal dysbiosis and perturbed barrier function. These findings support a model in which specific members of the intestinal microbiota promote colorectal carcinogenesis. Clinicians should evaluate patients with bacteremia from these species for neoplastic lesions in the colorectum.
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Patients with diabetic foot ulcers usually suffer from inefficient epithelisation and angiogenesis accompanied by chronic wound healing. Diabetic foot ulcers remain a major challenge in clinical ...medicine; however, traditional treatments are incapable of transdermal drug delivery, resulting in a low drug delivery rate. We report the development of Ti
C
MXenes-integrated poly-γ-glutamic acid (γ-PGA) hydrogel microneedles to release asiaticoside (MN-MXenes-AS). Asiaticoside was loaded into PGA-MXenes hydrogel to facilitate cell proliferation while regulating angiogenesis. The characterisation and mechanical strength of the microneedles were investigated in vitro, and the wound-healing efficacy of the microneedles was confirmed in diabetic mice. MXenes significantly improved the mechanical strength of microneedles, while γ-PGA hydrogels provided a moist microenvironment for wound healing. Mice treated with MN-MXenes-AS demonstrated obvious improvements in wound healing process. We successfully fabricated an MXenes-integrated microneedle that possesses sufficient rigidity to penetrate the cuticle for subcutaneous drug delivery, thereby accelerating diabetic wound healing. We demonstrated that MN-MXenes-AS is effective in promoting growth both in vivo and in vitro. Collectively, our data show that MN-MXenes-AS accelerated the healing of diabetic foot ulcers, supporting the use of these microneedles in the treatment of chronic wounds.
Template-driven strategy is widely explored for the synthesis of nano/micro materials. Of all the templates studied, naturally occurring biological systems such as proteins, viruses and bacteria have ...attracted more attention due to the prolific sources and complex structural diversities. Herein, we report a simple bacteria templated synthesis of silver microspheres over a bottom-up controlled route. These as-prepared silver microspheres not only have narrow size distribution but possess hollow and porous structures. Surface enhanced Raman scattering (SERS) experiments using 2-mercaptopyridine (2-Mpy) as probing molecules show that these hollow porous microspheres can act as excellent substrate for ultrasensitive detecting. The detection limit is as low as 10
−15
M and the enhancement factor reaches to 10
11
. Compared with other conventional SERS substrates, the reproducible, high sensitive and cost-effective Ag microspheres could become an ideal substrate choice for practical SERS application.
Hollow and porous silver microspheres are synthesized using bacteria as template. They have been proven to be excellent SERS substrate.
The localization of invisible and impalpable small pulmonary nodules has become an important concern during surgery, since current widely used techniques for localization have a number of ...limitations, such as invasive features of hookwires and microcoils, and rapid diffusion after injection of indocyanine green (ICG). Lanthanide-based metal-organic frameworks (MOFs) have been proven as potential fluorescent agents because of their prominent luminescent characteristics, including large Stokes shifts, high quantum yields, long decay lifetimes, and undisturbed emissive energies. In addition, lanthanides, such as Eu, can efficiently absorb X-rays for CT imaging. In this study, we synthesized Eu-UiO-67-bpy (UiO = University of Oslo, bpy = 2,2'-bipyridyl) as a fluorescent dye with a gelatin-methacryloyl (GelMA) hydrogel as a liquid carrier. The prepared complex exhibits constant fluorescence emission owing to the luminescent characteristics of Eu and the stable structure of UiO-67-bpy with restricted fluorescence diffusion attributed to the photocured GelMA. Furthermore, the hydrogel provides stiffness to make the injection site tactile and improve the accuracy of localization and excision. Finally, our complex enables fluorescence-CT dual-modal imaging of the localization site.
The use of a novel cytosensor, comprised of bio-mimetically synthesized Ag@BSA composite microspheres, for the detection of KB cells (a model system) is described. The Ag@BSA composite microspheres ...were immobilized on Au electrodes via Au-thiol bonds. Scanning electron microscopy (SEM), atomic force microscopy (AFM) and transmission electron microscopy (TEM) images revealed that the Ag@BSA were well-dispersed microspheres with an average diameter of 500nm, including the monolayer of BSA. The immobilization of Ag@BSA composite microspheres onto Au electrodes is thought to increase the electrode surface area and accelerate the electron transfer rate while providing a highly stable matrix for the convenient conjugation of target molecules (such as folic acid) and the prolonged incubation of cells. Cyclic voltammetry (CV) and electrochemical impedance spectroscopy (EIS) studies showed that the fabricated cytosensor was able to detect KB cells ranging from 6.0×101 to 1.2×108cellsmL−1 with a lower detection limit of 20cellsmL−1. Due to its facile synthesis, high stability and reproducibility and cytocompatibility, the novel cytosensor described here could find multifarious uses in applications, such as cancer diagnosis, drug screening and cell adhesion studies.
►·Ag@BSA composite microspheres were synthesized at room temperature through a biomimetic way. ►·The composites possessed both conductivity and biocompatibility. ►·The composites were immobilized onto Au electrode and conjugated FA as a cytosensor for recognizing cancer cells. ►·The cytosensor showed excellent sensitivity and specificity.
Altered microbiome composition and aberrant promoter hypermethylation of tumor suppressor genes (TSGs) are two important hallmarks of colorectal cancer (CRC). Here we performed concurrent 16S rRNA ...gene sequencing and methyl-CpG binding domain-based capture sequencing in 33 tissue biopsies (5 normal colonic mucosa tissues, 4 pairs of adenoma and adenoma-adjacent tissues, and 10 pairs of CRC and CRC-adjacent tissues) to identify significant associations between TSG promoter hypermethylation and CRC-associated bacteria, followed by functional validation of the methylation-associated bacteria.
Fusobacterium nucleatum and Hungatella hathewayi were identified as the top two methylation-regulating bacteria. Targeted analysis on bona fide TSGs revealed that H. hathewayi and Streptococcus spp. significantly correlated with CDX2 and MLH1 promoter hypermethylation, respectively. Mechanistic validation with cell-line and animal models revealed that F. nucleatum and H. hathewayi upregulated DNA methyltransferase. H. hathewayi inoculation also promoted colonic epithelial cell proliferation in germ-free and conventional mice.
Our integrative analysis revealed previously unknown epigenetic regulation of TSGs in host cells through inducing DNA methyltransferase by F. nucleatum and H. hathewayi, and established the latter as CRC-promoting bacteria. Video abstract.
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