Rare-earth nanomaterials are being widely applied in medicine as cytotoxicity agents, in radiation and photodynamic therapy, as drug carriers, and in biosensing and bioimaging technology. Terbium (Tb), a rare-earth element belonging to the lanthanides, has a long luminescent lifetime, large stock displacement, narrow spectral width, and biofriendly probes. In cancer therapy, cancer stem cell (CSC)-targeted treatment is receiving considerable attention due to these cells’ harmful characteristics. However, CSCs remain barely understood. Therefore, to effectively label and inhibit the growth of CSCs, we produced a nanocomplex in which TbPO4·H2O nanorods were double conjugated with CD133 and PD-L1 monoclonal antibodies. The Tb3+ nanomaterials were created in the presence of a soft template (polyethylene glycol 2000). The obtained nanomaterial TbPO4·H2O was hexagonal crystal and nanorod in shape, 40–80 nm in diameter, and 300–800 nm in length. The nanorods were further surfaced through tetraethyl orthosilicate hydrolysis and functionalized with amino silane. Finally, the glutaraldehyde-activated Tb3+ nanorods were conjugated with CD133 monoclonal antibody and PD-L1 monoclonal antibody on the surface to obtain the nanocomplex TbPO4·H2O@silica-NH2+mAb^CD133+mAb^PD-L1 (TMC). The formed nanocomplex was able to efficiently and specifically label NTERA-2 cells, a highly expressed CD133 and PD-L1 CSC cell line. The conjugate also demonstrated promising anti-CSC activity by significant inhibition (58.50%) of the growth of 3D tumor spheres of NTERA-2 cells (p < 0.05).
Black pepper ( Piper nigrum L.) is widely grown in the Chu-se district of Gia Lai province in Vietnam. The pepper, used as a spice, also serves as a traditional medicine in many countries. Black pepper contains many different substances; the most active of these is piperine, which exerts anti-oxidant, anti-inflammatory, and anti-cancer effects. However, piperine is a poorly absorbed alkaloid, and high concentrations may be toxic. Therefore, its medicinal uses remain limited. Here, we extracted piperine from black peppers collected at Chu Se, created piperine and anti-CD133 monoclonal antibodies (mAb^CD133) containing nanoliposomal complexes (PMCs), and evaluated their inhibitory effects on cancer stem cells (CSCs) in vitro. The physical properties of PMCs showed an approximated diamater of 170 nm, a PDI of 0.23, zeta potential of −9.38 mV, and an encapsulated efficiency of 73.33 ± 9.09%. The PMCs significantly inhibited NTERA-2 cell growth (IC50 = 435.3 ± 4.3 µM), but were not toxic to healthy cells (IC50 >500 µM). The PMCs remarkably affected the CSC surface marker expressed level of which the CD44+/CD133+ population was only 2.12% compared with 21.72% for blank nanoliposomes. The NTERA-2 antiproliferative activities of PMCs might be associated with their G2 cell cycle phase arresting and caspase-3 inducible activities (up to 1.51 times) ( P < 0.05). The nanoliposomal complex also significantly inhibited the proliferation of NTERA-2 cells in three dimensional tumorspheroids with an IC50 = 245.82 ± 11.44 µM and reduced the size by up to 41.50 ± 4.31% ( P < 0.05). Thus, the PMCs proved their enhanced potential biomedical and pharmacological applications in targeted cancer therapies.
Black pepper (Piper nigrum) is an autoicous and decorous vine cultivated in many local regions of Gia Lai. Black pepper is one of the most commonly consumed spices, and its pungency is due to the presence of alkaloids, such as piperine. This compound represents diverse biological activities, including anti-inflammatory, anticancer, antiviral, anti-larvicidal, pesticide, anti-alzheimer’s activities, etc. However, due to its poor solubility as well as its toxic effects at high use concentration, piperine is still in limit of pharmaceutical applications. In this study, we have used black pepper seed collected at Chu Se - Gia Lai to extract piperine. The compound extracted efficiency was approximately 18% with 96.7% of purity. Based on the obtained pure piperine, the hybrid nanopiperine-CD133 monoclonal antibody (mAb^CD133) complexes were fabricated with the nanoparticle size of about 170 nm, the polydispersity index (PDI) of 0.23 and the zeta potential of -9.4 mV. The nanocomplex was subjected for growth inhibitory activities against cancer colorectal cells (HT-29 cell line). The results showed that the nanopiperine-mAb^CD133 complex exhibited significant in vitro growth inhibition HT-29 colorectal cancer cells (46.56 ± 2.78%), while the viability of healthy cells remained unaffected (17.77 ± 0.82 %). The nanocomplex could also label 12.17% of HT-29 cells, which was rather higher than 3.83% from mAb^CD133 conjugated phycoerythrin (PE) as positive control. The fabricated nanopiperine-mAb^CD133 complex has proved the enhanced cytotoxic activities against colorectal cancerous cells as well as promising biopharmaceutical potency.
Nanotechnology is the key technology that brings many important applications in biomedical research.Nanolantanites present high stability, easy fabrication and functionalization. Tb3+ ion-containing nanomaterial, a specific type of nanolantanites, possess great prospects. In addition, cancer stem cells (CSCs) are directlyrelated to drug resistance, metastasis, recurrent cancer, etc. Therefore, CSCs are considered as the target forcancer researching and for discovery of more effective therapies. CD133, a trans-membrane glycoprotein, isone of the typical markers that are found to appear very commonly on the surface of many types of CSCs. Inthis study, CD133 monoclonal antibody (MAb) was cojugated with nanomaterials containing Tb3+. Thecoupling between fluorescented nanomaterials containing Tb3+ ions and CD133 MAb was then incubated withhuman colon cancer cells (HT-29) to evaluate its ability to label CSCs in vitro. The results showed thatnanorods containing rare-earth based Tb3+ ions which were fabricated by hydrothermal method, present thelength of about 300 - 800 nm and the diameter in range of 40 - 50 nm. The Tb3+ nanoparticals also havehexagonal structure of terbium phosphate monohydrate and green illuminant. Tb3+ nanorods were also furthersurface silica coated and amino-silane functionalized. This nanostructure was successfully combined withmonoclonal antibodies against CD133 which labelled the surface marker of HT-29 human colon cancer cells.As a result, the combination of CD133+TbPO4@Silica-NH2 (functionalized surface) showed strongerluminescence than the CD133+TbPO4 unfunctionalized combination.
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