Fabrication of ultrasmall single-component omnipotent nanotheranostic agents integrated with multimodal imaging and multiple therapeutic functions becomes more and more practically relevant but challenging. In this article, sub 10 nm Bi 2 S 3 biocompatible particles are prepared through a bovine serum albumin (BSA)-mediated biomineralization process under ambient aqueous conditions. Owing to the ultrasmall size and colloidal stability, the resulting nanoparticles (NPs) present outstanding blood circulation behavior and excellent tumor targeting ability. Toward theranostic applications, the biosafety profi le is carefully investigated. In addition, photothermal conversion is characterized for both photoacoustic imaging and photothermal treatment of cancers. Upon radiolabeling, the performance of the resulting particles for SPECT/CT imaging in vivo is also carried out. Additionally, different combinations of treatments are applied for evaluating the performance of the as-prepared Bi 2 S 3 NPs in photothermal-and radiotherapy of tumors. Due to the remarkable photothermal conversion effi ciency and large X-ray attenuation coeffi cient, the implanted tumors are completely eradicated through combined therapies, which highlights the potential of BSA-capped Bi 2 S 3 NPs as a novel multifunctional nanotheranostic agent.
. (2016). pH-responsive Fe(III)-gallic acid nanoparticles for in vivo photoacoustic imaging-guided photothermal therapy. Advanced Healthcare Materials, 5 (7), 772-780.
Colorectal cancer (CRC) is still one of the most important neoplasias causing human death. Multidisciplinary therapy has won consensus in the management of CRC, of which, radiotherapy occupies an important position. However, radioresistance is still a major obstacle in local control of CRC. Overexpression of long non-coding RNA HOTAIR has been found to correlate with tumorigenesis and poor prognosis in several types of cancer. In the present study, we analyzed HOTAIR expression levels of 53 CRC patients in tumor and adjacent normal tissue by real-time quantitative PCR. Knockdown of HOTAIR by RNA interference was performed to explore its roles in cell proliferation, migration, invasion, apoptosis and radiosensitivity. Results showed that CRC patients had higher HOTAIR expression in tumor tissues compared with adjacent normal tissues. In vitro, downregulation of HOTAIR reduced proliferation, migration and invasiveness while enhanced apoptosis and radio-sensitivity of CRC cells. Taken together, our findings suggest that long non-coding RNA HOTAIR expression is closely associated with tumor invasion and radiosensitivity, indicating the potential role in diagnostics and therapeutics of CRC.
Background: Exosomes are microvesicles secreted by body cells for intercellular communication. Circular RNA circ_0000338 was found to present in extracellular vesicles and improve the chemo-resistance of colorectal cancer (CRC) cells. However, the role of exosomal circ_0000338 in 5-Fluorouracil (5-FU)-resistance in CRC is largely unknown. Methods: The levels of circ_0000338, microRNA (miR)-217 and miR-485-3p were detected using the qRT-PCR. The IC50 values of cells to 5-FU, cell proliferation and apoptosis were evaluated using CCK-8, colony formation, flow cytometry and western blot assays. The interaction between miR-217 or miR-485-3p and circ_0000338 was confirmed by RIP, dual-luciferase reporter and pull-down assays. Exosomes were isolated by ultracentrifugation, and qualified by transmission electron microscopy (TEM), nanosight tracking analysis (NTA) and western blot. Xenograft models were performed to analyze whether circ_0000338 loaded exosomes could re-resist CRC cells to 5-FU in vivo. Results: Circ_0000338 was elevated in 5-FU-resistant CRC tissues and cells, and circ_0000338 knockdown sensitized 5-FU-resistant CRC cells to 5-FU through enhancing apoptosis and decreasing proliferation in vitro. Mechanistically, circ_0000338 directly bound to miR-217 and miR-485-3p, and the inhibition of miR-217 or miR-485-3p reversed the effects of circ_0000338 knockdown on cell 5-FU resistance in CRC. Additionally, extracellular circ_0000338 could be incorporated into secreted exosomes and transmitted to 5-FU-sensitive cells. Treatment-sensitive cells with exosomes containing circ_0000338 reduced 5-FU response in CRC both in vitro and in vivo. Besides that, exosomal circ_0000338 was higher in patients exhibiting resistance to 5-FU, and showed well diagnostic efficiency in 5-FU resistant CRC. Conclusion: The delivery of circ_0000338 via exosomes enhanced 5-FU resistance in CRC through negative regulation of miR-217 and miR-485-3p, indicating a promising diagnostic and therapeutic marker for 5-FU-based chemotherapy in CRC patients.
Autophagy is a double-edged sword in tumor development. Recent studies have found that miRNAs have an inhibitory effect on the regulation of autophagy. It has been reported that miR-31 plays an important role in the development of colorectal cancer. However, what role miR-31 plays in colorectal cancer-associated fibroblasts (CAFs) has not been determined. In this study, we confirmed that the expression of miR-31 in CAFs was higher than in normal colorectal fibroblasts (NFs). We also found that treatment of CAFs with miR-31 mimic inhibited the expression of the autophagy-related genes Beclin-1, ATG, DRAM and LC3. In addition, we found up-regulation of miR-31 significantly affected colorectal cancer cell behaviors, including proliferation, invasion and apoptosis. Also, up-regulation of miR-31 in CAF could increase the radiosensitivity of colorectal cancer cells co-cultured with CAF. In summary, miR-31 can inhibit autophagy in colorectal CAFs, affect colorectal cancer development, and increase the radiosensitivity of colorectal cancer cells co-cultured with CAF. We hypothesize that miR-31 may become a new target of treatments for colorectal cancer.
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