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In vivo Biodistribution and Highly Efficient Tumour Targeting of Carbon Nanotubes in Mice
Published in Lajos P. Balogh, Nano-Enabled Medical Applications, 2020
Zhuang Liu, Weibo Cai, Lina He, Nozomi Nakayama, Kai Chen, Xiaoming Sun, Xiaoyuan Chen, Hongjie Dai
U87MG human glioblastoma and HT-29 human colorectal cancer cell lines (from American Type Culture Collection, ATCC) were cultured under standard conditions. The U87MG and HT-29 tumour models were generated by subcutaneous injection of 5 × 106 cells in 50 µl PBS into the front left and front right legs of the×mice, respectively. The mice were used for the study when the tumour volume reached 200–300 mm3.
Conjugated Graphene Gold Nanocomposites for Cancer Therapy
Published in Devarajan Thangadurai, Saher Islam, Charles Oluwaseun Adetunji, Viral and Antiviral Nanomaterials, 2022
Zaira Zaman Chowdhury, Abu Nasser Faisal, Shahjalal Mohammad Shibly, Devarajan Thangadurai, Saher Islam, Jeyabalan Sangeetha
Several studies have been conducted on the photothermal characteristics of AuNPs and GO as independent entities, and both AuNPs and GO have demonstrated impressive photothermal efficacy in vivo and in vitro (Xu et al. 2013; Turcheniuk et al. 2015; Tomasella et al. 2020). However, in order to have these qualities, GO must be reduced. This is because GO has a strongly oxidized framework with a disordered conjugation, which decreases its conductance (Robinson et al. 2011; Khan et al. 2017). The photothermal feature of AuNRs is a result of the plasmonic interaction that exists on their surface. Several studies have been conducted on the coupling of AuNPs with GO to achieve effective photothermal characteristics (Lim et al. 2013; Dembereldorj et al. 2014; Song et al. 2015; Zhang et al. 2018). Earlier studies showed the photothermal effect of AuNPs–PEG–GO nanocomposites on A431 cells by exposing them to ultraviolet light (Dembereldorj et al. 2014). When subjected to a laser for 5 minutes, it was discovered that the AuNPs–PEG–GO generated heat. When exposed to light, this nanocomposite was capable of reducing dramatically the number of cells in the test tube by 40% (Dembereldorj et al. 2014). rGO–AuNPs shown superior photothermal properties when compared to untreated AuNPs, noncoated Au nano shells, and rGO–AuNOs nano shells (Lim et al. 2013). The feasibility of PEG-functionalized rGO–PEG coated with Au nano rods were coupled with Tat protein for the photothermal killing of the cancerous cells (Turcheniuk et al. 2016). The Tat protein was utilized to improve the target selectivity of the synthesized composite. In vivo experiments revealed that the combination was effective in inhibiting the proliferation of the U87MG tumour cells in mice (Turcheniuk et al. 2016).
Anti-Cancer Agents from Natural Sources
Published in Rohit Dutt, Anil K. Sharma, Raj K. Keservani, Vandana Garg, Promising Drug Molecules of Natural Origin, 2020
Debasish Bandyopadhyay, Felipe Gonzalez
Diphtheria toxins (DT) are secreted by the Corynebacterium dipheriae, a gram-positive bacterium that is known to cause an infectious disease known as diphtheria. This toxic substance is encoded by a tox gene, which is caused by a bacteriophage, that lives inside certain bacteria. To produce DT, a C.diphtheriae bacterium needs to contain the tox+ phages. Recent studies have evaluated mutated DT to validate its anticancer activity. In vivo evaluation was reported (Lubran et al., 1988)to validate the effects of CRM197, a mutated DT carrier protein that is often used for vaccines, on human adrenocortical carcinoma. CRM197 could bind to heparin-binding EGF-like growth factor (HB-EGF), which is common in adrenocortical carcinomas. By binding to HB-EGF, CRM197 reduced angiogenesis and initiated apoptosis. Notably, CRM197 also inhibited cancerous cell migration (Lubran, 1988) that prevented metastasis. Another study (Zhang et al., 2010) carried out by using a DT mutant DT385, in vivo on chick chloroallantoic membrane (CAM), Lewis lung cancer (LLC) mouse model, and 18 different cancer cells. DT385 inhibited angiogenesis in CAM but were resistant to endothelial cells. In LLC cells, the subcutaneous growth was slightly inhibited. The tumor size reduced meaningfully. DT385 showed mild to strong sensitivity in 15 out of 18 tested cancer cell types. Human malignant cell lines U-87 MG (glioma), HEK293 (kidney), Hela (cervical), Calu-3 (lung), U251 (glioblastoma), and 293T (lung) showed high sensitivity to DT385. Moderate sensitivity was noted in MDA-MB-231 (breast), Colo201 (colon), Colo205 (colon), PC-3 (prostate), HT1080 (fibrosarcoma), and LNCap (prostate). Weakly sensitive cell lines were MCF7 (breast), HCT116 (colon/rectum), Hep3 (cervical), NB4 (promyelocytic leukemia), HL-60 (myeloid leukemia), and BT-20 (breast) (Zhang et al., 2010). DT385 prevents cell proliferation by inducing apoptosis.
Sonodynamic therapy of glioblastoma mediated by platelets with ultrasound-triggered drug release
Published in Drug Delivery, 2023
Meiyao Wang, Huazhen Xu, Tongfei Li, Ke Li, Quan Zhang, Siyi Chen, Li Zhao, Jincao Chen, Xiao Chen
Drug-loaded platelets in suspension (2 × 105 IOPD-Ce6@Plt in 1 mL of PBS) were added into a 3.5-cm petri dish with U87MG cells (2 × 106) with 80% confluence and the mixture was immediately irradiated with ultrasound (1 MHz, 0.5 W/cm2, 30 s) and then subjected to time-lapse fluorescence microscopy. Alternatively, the mixture was maintained for 60 min before taking out for flow cytometry analysis of drug fluorescence in the U87-MG cells. To evaluate IOPD-Ce6@Plt-mediated sonodynamic toxicity to the U87-MG cells, the mixture of IOPD-Ce6@Plt and U87-MG was ultrasound-irradiated (1 MHz, 0.5 W/cm2, 30 s) and the culture media was replaced with fresh culture medium an hour later. A second time of UI (1 MHz, 1 W/cm2, 30 s) was then applied to the U87MG cells. The U87MG cells were either immediately taken out for detection of intracellular ROS generation, or taken out 6 h later for evaluation of cell viability, DNA damage, and cell death. 2′,7′-dichlorofluorescin diacetate (DCFDA) staining and flow cytometry were used to measure ROS generation. Rhodamine 123 labeling and flow cytometry were used to measure cell viability. DNA damage was evaluated by western blotting analysis of phospho-ataxia telangiectasia mutated kinase (p-ATM) and H2A histone family member X (γ-H2AX). Annexin-v labeling and flow cytometry were used to measure cell death.
Evaluation of 99mTc-HYNIC-(ser)3-LTVPWY peptide for glioblastoma imaging
Published in International Journal of Radiation Biology, 2020
Shima Shahsavari, Zahra Shaghaghi, Seyed Mohammad Abedi, Seyed Jalal Hosseinimehr
The binding affinity of radiolabeled peptide to U-87 MG cells for calculation of dissociation constant (Kd) and total number of binding sites per cell (Bmax) were examined by saturation binding experiment as described previously (Khodadust et al. 2018). In the brief, U-87 MG cells were seeded at a density of 2.5 × 105 cells per well in 24-well tissue culture plates and allowed to attach overnight. On the next day, cells were incubated for 2 h at 37 °C with increasing concentrations of radiolabeled peptide (0.1, 0.5, 1, 2.5, 5, 25, and 50 nM). One dish was used as a blocking sample and parallel incubations were conducted in the presence of the highest concentration (500-fold excess) of non-labeled peptide. Three dishes were used for each concentration. At the end of the incubation period, medium was removed and cells were tripsinized and collected for measuring activity by a gamma counter. The equilibrium dissociation constant (KD) and number of binding sites (Bmax) of the receptor were determined using Prism 5 software (Version 5.04.2010).
Cytotoxicity, dose-enhancement and radiosensitization of glioblastoma cells with rare earth nanoparticles
Published in Artificial Cells, Nanomedicine, and Biotechnology, 2019
Victor M. Lu, Felicity Crawshay-Williams, Benjamin White, Amy Elliot, Mark A. Hill, Helen E. Townley
RE nanoparticles were added at 40 μM to the cell culture media, and cells incubated overnight. Cells were then irradiated at either 0 or 3 Gy. The media was then removed, and cells washed with PBS. Cells were then removed from the flasks using trypsin and cell number ascertained using a haemocytometer. Cells were added to the wells in triplicate for each treatment. (Results showed that 500 cells for U-87 MG, and 750 cells for Mo59K cells, were appropriate starting cultures). The cells were incubated for at least two weeks at 37 °C in a 5% CO2 atmosphere. Subsequently cells were stained for counting. Firstly, media was removed and cells washed with PBS. Cells were then fixed with glutaraldehyde for 30 min. Cells were then stained with crystal violet solution for at least 1 h. The cells were then washed with water and left to dry prior to counting.