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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 (IC 50  = 435.3 ± 4.3 µM), but were not toxic to healthy cells (IC 50  &gt;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 &lt; 0.05). The nanoliposomal complex also significantly inhibited the proliferation of NTERA-2 cells in three dimensional tumorspheroids with an IC 50  = 245.82 ± 11.44 µM and reduced the size by up to 41.50 ± 4.31% ( P &lt; 0.05). Thus, the PMCs proved their enhanced potential biomedical and pharmacological applications in targeted cancer therapies.

The Improved Anticancer Activities of Piperine Nanoliposome Conjugated CD133 Monoclonal Antibody Against NTERA-2 Cancer Stem Cells