Although doxorubicin has become a key drug in cancer treatment, the resistance of colorectal carcinoma to doxorubicin is a major problem in clinical practice. F-box and WD repeat domain-containing 7 (FBXW7) plays important roles in human cancers and is one of the major causes of drug resistance. The miR-223/FBXW7 pathway has been reported to be a crucial clue to the mechanism of chemoresistance in many human cancers, such as gastric cancer, breast cancer, and non-small cell lung cancer. However, it is unclear whether similar mechanisms of doxorubicin resistance are involved in colorectal cancer (CRC). The aim of the current study was to evaluate the role of miR-223/FBXW7 pathway in chemosensitivity in different CRC cell lines and to investigate the relevant underlying mechanisms. We found that high levels of FBXW7 expression were associated with increased doxorubicin sensitivity in different CRC cell lines, and FBXW7 was regulated by miR-223. Overexpression of miR-223 decreased FBXW7 expression and the sensitivity of CRC cells to doxorubicin, while suppression of miR-223 had the opposite effect. Moreover, epithelial–mesenchymal transition (EMT) was proved to be regulated by miR-223/FBXW7 pathway and involved in the drug resistance. In conclusion, miR-223/FBXW7 axis regulates doxorubicin sensitivity through EMT in CRC, which may lead to the development of individualized treatment in clinical practice.
25 April 2021 in Journal of Biomaterials Applications
In this experiment, a new amphiphilic chitosan-poly(lactide) graft copolymer was synthesized and characterized by IR, 1H-NMR, XRD, TGA. The obtained chitosan-poly (lactide) graft copolymer was used as the matrix material to prepare nanodroplets (NDs) encapsulating with liquid PFP by double-emulsion and solvent evaporation method. The resulting NDs were characterized by photon correlation spectroscopy and transmission electron microscopy (TEM). The biocompatibility was explored by cytotoxicity assay, cell migration assay and blood biochemistry analysis. The experiments of ultrasonic imaging in vitro and in vivo were carried out with a B-mode clinical ultrasound imaging system. The results of FI-IR and 1H-NMR confirmed the successful grafting reaction of polylactic acid(PLLA) to chitosan with a graft rate of 365%. The average size of the NDs was 101.1 ± 2.7 nm, with the polydispersity index (PDI) of 0.127 ± 0.020, and the zeta potential was −31.8 ± 1.5 mV. From the TEM results, NDs were highly dispersed and had a spherical shape with a distinct capsule structure. The NDs exhibited good stability during storage at 4°C. The NDs solution with different concentrations did not affect cell growth and showed good biocompatibility in cytotoxicity, cell migration and blood biochemistry studies. Under the irradiation of ultrasonic waves, the NDs formed an ultrasonic high signal, which could significantly enhance the ultrasound imaging of tumor tissue in vivo. Taken together, the NDs hold great potential for ultrasound imaging as a nanosized contrast agent.
7 December 2020 in Journal of Biomaterials Applications
The proposed study was to develop the preparation of ultrasmall superparamagnetic iron oxide nanoparticles (USPIONs) modified with citric acid, with surface conjugated with lactoferrin (Lf), which used as a potential targeted contrast agent for magnetic resonance imaging (MRI) of brain glioma. USPIONs were prepared by the thermal decomposition method. The hydrophobic USPIONs were coated with citric acid by the ligand exchange method. Then, Lf was conjugated into the surface of USPIONs. The obtained Lf-USPIONs were analyzed by fourier transform infrared (FTIR) spectroscopy and polyacrylamide gel electrophoresis. The size, size distribution, shape and superparamagnetic property of Lf-USPIONs were investigated with TEM and vibrating sample magnetometer (VSM). Both FTIR and electrophoresis analysis demonstrated the successful conjugation of Lf to the surface of USPIONs. The average size of Lf-USPIONs was about 8.4 ± 0.5 nm, which was determined using the statistics of measured over 100 nanoparticles in the TEM image, with a negative charge of −7.3 ± 0.2 mV. TEM imaging revealed that Lf-USPIONs were good in dispersion and polygonal in morphology. VSM results indicated that Lf-USPIONs were superparamagnetic and the saturated magnetic intensity was about 69.8 emu/g. The Lf-USPIONs also showed good biocompatibility in hemolysis, cytotoxicity, cell migration and blood biochemistry studies. MR imaging results in vitro and in vivo indicated that Lf-USPIONs exhibited good negative contrast enhancement. Taken together, Lf-USPIONs hold great potential for brain gliomas MR imaging as a nanosized targeted contrast agent.
1 August 2021 in Journal of Biomaterials Applications
Due to the low bioavailability and severe toxic side effects caused by the lack of selectivity of traditional chemotherapy drugs, the targeted delivery of chemotherapy drugs has become the key to tumor treatment. The activity and transmembrane potential of mitochondria in cancer cells were significantly higher than that of normal cells, making them a potential target for chemotherapeutic drug delivery. In this study, triphenylphosphine (TPP) based mitochondria targeting polylactic acid (PLLA) nanoparticles (TPP-PLLA NPs) were synthesized to improve the delivery efficiency of anticancer drugs. The carrier material was characterized by 1H NMR and FT-IR and 7-hydroxyl coumarin (7-HC) was successfully loaded into TPP-PLLA to form 7-HC/TPP-PLLA NPs. Further studies showed that TPP-PLLA NPs were primarily accumulated in the mitochondrial and 7-HC/TPP-PLLA NPs had higher antitumor activity. Taken together, our results indicated that TPP-PLLA NPs could be a promising mitochondria-targeted drug delivery system for cancer therapy.
Given that cancer mortality is usually due to a late diagnosis, early detection is crucial to improve the patient’s results and prevent cancer-related death. Imaging technology based on novel nanomaterials has attracted much attention for early-stage cancer diagnosis. In this study, a new block copolymer, poly(ethylene glycol)-poly(l-lactide) diblock copolymer (PEG-PLLA), was synthesized by the ring-opening polymerization method and thoroughly characterized using Fourier transform infrared spectroscopy (FT-IR), proton nuclear magnetic resonance spectroscopy (H-NMR), X-ray diffraction (XRD), and thermogravimetric analysis (TGA). The obtained PEG-PLLA was used to prepare nanoparticles encapsulated with perfluoropentane and salicylic acid by the emulsion-solvent evaporation method, resulting in a new dual-mode nano-image probe (PEG-PLLA@SA·PFP). The zeta potential and mean diameter of the obtained nanoparticles were measured using dynamic light scattering (DLS) with a Malvern Zetersizer Nano. The in vitro biocompatibility of the PEG-PLLA nanoparticles was evaluated with cell migration, hemolysis, and cytotoxicity assays. Ultrasonic imaging was performed using an ultrasonic imaging apparatus, and chemical exchange saturation transfer (CEST) MRI was conducted on a 7.0 T animal scanner. The results of IR and NMR confirmed that the PEG-PLLA was successfully synthesized. The particle size and negative charge of the nanoparticles were 223.8 ± 2.5 nm and −39.6 ± 1.9 mV, respectively. The polydispersity of the diameter was 0.153 ± 0.020. These nanoparticles possessed good stability at 4 °C for about one month. The results of cytotoxicity, cell migration, and hemolysis assays showed that the carrier material was biocompatible. Finally, PEG-PLLA nanoparticles were able to significantly enhance the imaging effect of tumors by the irradiation of ultrasound and saturation by a radiofrequency pulse, respectively. In conclusion, these nanoparticles exhibit promising dual-mode capabilities for US/CEST MR imaging.
1 May 2024 in International Journal of Nanomedicine
Background: Medical imaging modalities, such as magnetic resonance imaging (MRI), ultrasound, and fluorescence imaging, have gained widespread acceptance in clinical practice for tumor diagnosis. Each imaging modality has its own unique principles, advantages, and limitations, thus necessitating a multimodal approach for a comprehensive disease understanding of the disease process. To enhance diagnostic precision, physicians frequently integrate data from multiple imaging modalities, driving research advancements in multimodal imaging technology research. Methods: In this study, hematoporphyrin-poly (lactic acid) (HP-PLLA) polymer was prepared via ring-opening polymerization and thoroughly characterized using FT-IR, 1H-NMR, XRD, and TGA. HP-PLLA based nanoparticles encapsulating perfluoropentane (PFP) and salicylic acid were prepared via emulsion-solvent evaporation. Zeta potential and mean diameter were assessed using DLS and TEM. Biocompatibility was evaluated via cell migration, hemolysis, and cytotoxicity assays. Ultrasonic imaging was performed with a dedicated apparatus, while CEST MRI was conducted using a 7.0 T animal scanner. Results: We designed and prepared a novel dual-mode nanoimaging probe SA/PFP@HP-PLLA NPs. PFP enhanced US imaging, while salicylic acid bolstered CEST imaging. With an average size of 74.43 ± 1.12 nm, a polydispersity index of 0.175 ± 0.015, and a surface zeta potential of − 64.1 ± 2.11 mV. These NPs exhibit excellent biocompatibility and stability. Both in vitro and in vivo experiments confirmed the SA/PFP@HP-PLLA NP’s ability to improve tumor characterization and diagnostic precision. Conclusion: The SA/PFP@HP-PLLA NPs demonstrate promising dual-modality imaging capabilities, indicating their potential for preclinical and clinical use as a contrast agent.