Microstructure Sensitivity on Environmental Embrittlement of a High Nb Containing TiAl Alloy under Different Atmospheres.

Mechanical properties in different atmospheres, including oxygen, vacuum, air and H2, of high Nb containing TiAl alloys with the compositions of Ti-45Al-8.5Nb-(0.2W, 0.2B, 0.02Y) have been investigated in this work. Three different microstructure types, nearly lamellar, gamma phase increased nearly lamellar and fully lamellar are selected for revealing the microstructure sensitivity of environmental embrittlement. The results show that the three types of microstructures are all affected by the hydrogen-induced environmental embrittlement. Although the fracture mode of the experimental alloy is cleavage fracture in all atmospheres, the proportions of transgranular and intergranular fractures are different, especially comparing the fracture surfaces in oxygen and hydrogen. Performance comparison results show that the nearly lamellar microstructure is the most susceptible to the hydrogen-induced environmental embrittlement, while the gamma phase increased microstructure is the most stable one; the fully lamellar microstructure results in moderate susceptibility to the atmospheres. Combined with the hydrogen absorption kinetic analysis, it indicates that γ phase at the interface of lamellar colony significantly inhibits the hydrogen-induced environmental embrittlement, while the effect of ß phase is just the opposite. In addition, the correlation between microstructure and hydrogen-induced environmental embrittlement is revealed and the corresponding mechanism is also discussed in this work.

Folic Acid-Modified Fluorescent-Magnetic Nanoparticles for Efficient Isolation and Identification of Circulating Tumor Cells in Ovarian Cancer.

Ovarian cancer (OC) is a lethal disease occurring in women worldwide. Due to the lack of obvious clinical symptoms and sensitivity biomarkers, OC patients are often diagnosed in advanced stages and suffer a poor prognosis. Circulating tumor cells (CTCs), released from tumor sites into the peripheral blood, have been recognized as promising biomarkers in cancer prognosis, treatment monitoring, and metastasis diagnosis. However, the number of CTCs in peripheral blood is low, and it is a technical challenge to isolate, enrich, and identify CTCs from the blood samples of patients. This work develops a simple, effective, and inexpensive strategy to capture and identify CTCs from OC blood samples using the folic acid (FA) and antifouling-hydrogel-modified fluorescent-magnetic nanoparticles. The hydrogel showed a good antifouling property against peripheral blood mononuclear cells (PBMCs). The FA was coupled to the hydrogel surface as the targeting molecule for the CTC isolation, held a good capture efficiency for SK-OV-3 cells (95.58%), and successfully isolated 2-12 CTCs from 10 OC patients' blood samples. The FA-modified fluorescent-magnetic nanoparticles were successfully used for the capture and direct identification of CTCs from the blood samples of OC patients.

Circulating tumor cells in colorectal cancer in the era of precision medicine.

Colorectal cancer (CRC) is one of the main causes of cancer-related morbidity and mortality across the globe. Although serum biomarkers such as carcinoembryonic antigen (CEA) and carbohydrate antigen 19-9 (CA-199) have been prevalently used as biomarkers in various cancers, they are neither very sensitive nor highly specific. Repeated tissue biopsies at different times of the disease can be uncomfortable for cancer patients. Additionally, the existence of tumor heterogeneity and the results of local biopsy provide limited information about the overall tumor biology. Against this backdrop, it is necessary to look for reliable and noninvasive biomarkers of CRC. Circulating tumor cells (CTCs), which depart from a primary tumor, enter the bloodstream, and imitate metastasis, have a great potential for precision medicine in patients with CRC. Various efficient CTC isolation platforms have been developed to capture and identify CTCs. The count of CTCs, as well as their biological characteristics and genomic heterogeneity, can be used for the early diagnosis, prognosis, and prediction of treatment response in CRC. This study reviewed the existing CTC isolation techniques and their applications in the clinical diagnosis and treatment of CRC. The study also presented their limitations and provided future research directions.

Synthesis of Au@MOF core-shell hybrids for enhanced photodynamic/photothermal therapy.

Photodynamic/photothermal therapy (PDT/PTT) has become a research focus of cancer treatment due to the non-invasiveness, spatio-temporal controllability, and effectiveness of repeated treatment. Here, Au@MOF core-shell hybrids were designed and constructed by the layer-by-layer method, and the thickness of the MOF shell can be adjusted by controlling the coordination reaction between the layers. Au nanorod cores mainly produce the PTT effect due to their strong absorbance at 650 nm. The porphyrin ligand in the MOF shell can convert O2 into 1O2 under light conditions, resulting in a high PDT effect. Moreover, the metal node Fe3O(OAc)6(H2O)3+ cluster of the MOF can catalyze the decomposition of H2O2 into O2 to overcome the hypoxic environment of tumors, which further improves the effect of PDT. The combination of the porphyrin ligand in the MOF structure and Au nanorods has promoted the synergistic effects of PDT/PTT. As expected, the results confirmed that Au@MOF hybrids showed no obvious biotoxicity in both cells and animal experiments, and exhibited good biocompatibility. With the synergistic effects of PDT/PTT, cancer cells could be effectively killed and tumor growth could be inhibited. In addition, the modification of folic acid on the surface of Au@MOF can further enrich the hybrids at the tumor site and enhance the inhibitory effect on tumors. These studies have proved that PDT and PTT can be effectively combined and have greater advantages in enhancing the treatment of tumors.

Selective capture of circulating tumor cells by antifouling nanostructure substrate made of hydrogel nanoparticles.

The detection and analysis of circulating tumor cells (CTCs) from cancer patients' blood samples present a powerful means to monitor cancer progression. In this work, an antifouling nanostructure substrate made of hydrogel nanoparticles was fabricated for an effective capture of CTCs from the blood samples. The hydrogel nanoparticles were synthesized by zwitterionic sulfobetaine methacrylate (SBMA), methacrylic acid (MAA) and N, N'-methylene bisacrylamide (MBA) through a simple polymerization. SBMA could provide an effective antifouling layer for the substrate to prevent nonspecific cell adhesion, MAA could afford active carboxyl groups for the immobilization of antibody to achieve specific CTC capture, and the nanostructured surface could improve the interaction of the target cells with the antibody modified substrate surface to enhance the capture efficiency of CTCs. Moreover, it was not necessary to further modify the antifouling molecules on the hydrogel nanoparticle substrate's surface, reducing the complexity and difficulty of the substrate preparation. The results showed that about 87 % of target cells (MCF-7 cells) were captured on the antibody modified hydrogel nanoparticle substrate. In contrast, the substrate showed little adhesive capacity for the nonspecific cells (K562 cells), and only 0.15 % of cells were captured. And 98 % of the captured cells kept good cell viability. Finally, 1-32 CTCs/mL were detected from the blood samples of five cancer patients, while no CTC was found in five healthy samples. It is envisaged that the new hydrogel nanostructure substrate is capable of capturing CTCs efficiently and specifically from patient blood samples to be used in cancer treatment.

A PLGA nanofiber microfluidic device for highly efficient isolation and release of different phenotypic circulating tumor cells based on dual aptamers.

The isolation of specific and sensitive circulating tumor cells (CTCs) is significant for applying them in cancer diagnosis and monitoring. In this work, dual aptamer-modified poly(lactic-co-glycolic acid) (PLGA) nanofiber-based microfluidic devices were fabricated to achieve the highly efficient capture and specific release of epithelial and mesenchymal CTCs of ovarian cancer. Dual aptamer targeting epithelial cell adhesion molecules (EpCAM) and N-cadherin proteins to improve the capture sensitivity, bovine serum albumin (BSA) to guarantee the capture purity and the nanofibers to increase the capture efficiency via synchronously and effectively capturing the epithelial and mesenchymal CTCs with good capture specificity and sensitivity from blood samples were used. We used the target cells including the ovarian cancer A2780 cells (N-cadherin-high, EpCAM-low) and OVCAR-3 cells (EpCAM-high, N-cadherin-low) to test the devices, which exhibited good capture efficiency (91% for A2780 cells, 89% for OVCAR-3 cells), release efficiency (95% for A2780 cells, 88% for OVCAR-3 cells), and sensitivity for rare cells (92% for A2780 cells, 88% for OVCAR-3 cells). Finally, the clinical blood samples of ovarian cancer patients were detected by the PLGA nanofiber-based microfluidic device, and 1 to 13 CTCs were successfully confirmed to be captured with the help of immunofluorescence staining identification. The results exhibited that the dual aptamer-modified PLGA nanofiber-based microfluidic device used as a tool for CTC capture has the potential for clinical application to guide the diagnosis, treatment, and prognosis of ovarian cancer patients.

Tannic Acid (TA)-Functionalized Magnetic Nanoparticles for EpCAM-Independent Circulating Tumor Cell (CTC) Isolation from Patients with Different Cancers.

The majority of current methods of isolating circulating tumor cells (CTCs) rely on a biomarker. However, the isolation efficiency may be compromised due to the heterogeneity of CTCs. In this work, a simple and broad-spectrum method is established to efficiently isolate the heterogeneous CTCs from patient blood samples using tannic acid (TA)-functionalized magnetic nanoparticles (MNPs). The TA-functionalized MNPs (MNPs-TA) inhibit the nonspecific adhesion of peripheral blood mononuclear cell (PBMC) and enhance cancer cell capture, resulting from the unique interaction between TA and glycocalyx on cancer cells. The MNPs-TA was demonstrated to effectively capture seven kinds of cancer cells (HeLa, PC-3, T24, MAD-MB-231, MCF-7, HT1080, A549) from artificial samples (62.3-93.7%). Moreover, this epithelial cell adhesion molecule (EpCAM)-independent CTC isolation method was also tested using clinical blood samples from patients with different cancers (21 patients), which may provide a universal tool to detect CTCs in the clinic.

Antifouling hydrogel-coated magnetic nanoparticles for selective isolation and recovery of circulating tumor cells.

For reliable downstream molecular analysis, it is crucially important to recover circulating tumor cells (CTCs) from clinical blood samples with high purity and viability. Herein, magnetic nanoparticles coated with an antifouling hydrogel layer based on the polymerization method were developed to realize cell-friendly and efficient CTC capture and recovery. Particularly, the hydrogel layer was fabricated by zwitterionic sulfobetaine methacrylate (SBMA) and methacrylic acid (MAA) cross-linked with N,N-bis(acryloyl)cystamine (BACy), which could not only resist nonspecific adhesion but also gently recover the captured cells by glutathione (GSH) responsiveness. Moreover, the anti-epithelial cell adhesion molecule (anti-EpCAM) antibody was modified onto the surface of the hydrogel to provide high specificity for CTC capture. As a result, 96% of target cells were captured in the mimic clinical blood samples with 5-100 CTCs per mL in 25 min of incubation time. After the GSH treatment, about 96% of the obtained cells were recovered with good viability. Notably, the hydrogel-coated magnetic nanoparticles were also usefully applied to isolate CTCs from the blood samples of cancer patients. The favorable results indicate that the hydrogel-modified magnetic nanoparticles may have a promising opportunity to capture and recover CTCs for subsequent research.

Cationic superabsorbent hydrogel composed of mesoporous silica as a potential haemostatic material.

The control of massive bleeding and its related wound infection is the main challenge for both military and civilian trauma centres. In this study, a cationic superabsorbent hydrogel coordinated by mesoporous silica (CSH-MS) was synthesized by free-radical polymerization for both haemostasis and antibacterial use. The as-prepared CSH-MS has a rough surface, and its water absorption is approximately 5000%. The resultant CSH-MS1 could promote blood cell aggregation and facilitate plasma protein activation via haemadsorption, resulting in efficient blood clot formation. Furthermore, CSH-MS1 (with approximately 5.06% contents of MS) dramatically reduces bleeding time and reduces blood loss in a rat-tail amputation model. Moreover, the CSH-MSs exhibits good antibacterial activities, excellent cytocompatibility and negligible haemolysis. Therefore, CSH-MS can serve as a novel type of haemostatic material in clinical applications.

Fabrication of aptamer modified TiO2 nanofibers for specific capture of circulating tumor cells.

Herein, we developed an inexpensive titanium dioxide (TiO2) nanofiber substrate for efficient and selective capture of circulating tumor cells (CTCs) from mimic patients' samples. The TiO2 nanofiber substrates were fabricated by electrospinning in combination with the calcination process. The surface of nanofiber substrates was modified with the anti-adhesion molecule, bovine serum albumin (BSA) and the nucleolin aptamer AS1411, wherein, aptamer AS1411 specifically binds to the nucleolin protein overexpressed on the membrane surface of cancer cells. The formed TiO2 nanofiber substrates exhibited high efficacy and specificity to capture nucleolin positive cells through synergistic topographic interactions. Using the rare number of cell capture experiments, the capture efficiency of up to 75 % was achieved on the surface of the nanofiber substrate for rare number target cells spiked in the white blood cells (WBCs) from 1 mL whole blood samples. In conclusion, this study highlighted the potential of the TiO2-BSA-biotin-AS1411 nanofiber substrate as a highly efficient platform to realize the selective and specific capture of rare CTCs in the clinical settings.

Natural Biointerface Based on Cancer Cell Membranes for Specific Capture and Release of Circulating Tumor Cells.

Circulating tumor cells (CTCs) are an important part of liquid biopsy as they represent a potentially rich source of information for cancer diagnosis, monitoring, prognosis, and treatment guidance. It has been proved that the nanotopography interaction between cells and the surface of CTC detection platforms can significantly improve the capture efficiency of CTCs, whereas many mature nanostructure substrates have been developed based on chemistry materials. In this work, a natural biointerface with unique biological properties is fabricated for efficient isolation and nondestructive release of CTCs from blood samples using the cancer cell membranes. The cell membrane interfaces are proved to have a good antiadhesion property for nonspecific cells because of their own electronegativity. A natural surface nanostructure is provided by the cancer cell membrane to nicely match with the surface nanotopography of CTCs. Bovine serum albumin (BSA) as a linker and DNA aptamer against the epithelial cell adhesion molecule (EpCAM) as a specific affinity molecule are then introduced onto the cell membrane interfaces to achieve the highly efficient and specific capture of CTCs. Finally, the captured target cells can be intactly released from the substrate using the complementary DNA sequence with controlling the incubation time. This study provides a smart strategy in the development of a natural biological interface for the isolation and release of CTCs with high purity.

Aptamer-based nanostructured interfaces for the detection and release of circulating tumor cells.

Analysis of circulating tumor cells (CTCs) can provide significant clinical information for tumors, which has proven to be helpful for cancer diagnosis, prognosis monitoring, treatment efficacy, and personalized therapy. However, CTCs are an extremely rare cell population, which challenges the isolation of CTCs from patient blood. Over the last few decades, many strategies for CTC detection have been developed based on the physical and biological properties of CTCs. Among them, nanostructured interfaces have been widely applied as CTC detection platforms to overcome the current limitations associated with CTC capture. Furthermore, aptamers have attracted significant attention in the detection of CTCs due to their advantages, including good affinity, low cost, easy modification, excellent stability, and low immunogenicity. In addition, effective and nondestructive release of CTCs can be achieved by aptamer-mediated methods that are used under mild conditions. Herein, we review some progress in the detection and release of CTCs through aptamer-functionalized nanostructured interfaces.