A New Liposomal Formulation of Hydrogenated Anacardic Acid to Improve Activities Against Cancer Stem Cells

Le Tri Vien, Nguyen Thi Nga, Phung Thi Kim Hue, Tran Hoang Bao Kha, Nguyen Hong Hoang, Pham Thi Hue, Pham Ngoc Thien, Chi Ying F. Huang, Phan Van Kiem*, Do Thi Thao

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review


Anacardic acid (AA) is a natural active ingredient that accounts for 65% of the liquid extract from the shell of the cashew nut. Due to the stronger cytotoxic activity of hydrogenated AA (HAA) against NTERA-2 cancer stem cells (CSCs) than AA itself, HAA was co-conjugated with CD133 monoclonal antibody (mAb^CD133) into nanoliposomal particles (AMC). This nanoliposomal complex is expected to improved HAA activities against CSCs based on the targeting capacity of mAb^CD133 toward CD133, a typical CSCs’ surface marker. AMC was manufactured with a mean size of 100.9 nm, a zeta potential of −40.7 mV, and a PDI of 0.283. We report a 100% encapsulation efficiency of HAA into liposomes and a 90.7% conjugation efficiency with mAb^CD133. The penetration of AMC into NTERA-2 CSCs after 2 h was 83.7%. The AMC complex inhibited NTERA-2 growth with an IC50 (inhibition concentration at 50%) value of 75.83 ± 6.70 µM, showing the targeting ability and lower toxicity (IC50 > 100 µM) on healthy cells. The AMC nanoparticles also demonstrated significant potential apoptotic induction by activating caspase 3 activity by up to 2.57 and 2.06 folds compared to that of the negative control at 20 and 4 µM, respectively. This induction was significant improvement in comparison with that of unconjugated HAA (P <.05). AMC presented a clear effect on the solid structure of NTERA-2 spheroids and significantly suppressed the proliferation of CSCs in the 3D tumorspheres with an IC50 = 64.25 ± 3.15 µM, compared to the free form with an IC50 = 82.22 ± 0.65 µM (P <.05). Therefore, this nanoliposomal complex exhibits promising capacities as an effective material against NTERA-2 CSCs.

Original languageEnglish
JournalNatural Product Communications
Issue number6
StatePublished - Jun 2022


  • AMC
  • cancer stem cell
  • cashew nut shell
  • CD133 monoclonal antibody
  • hydrogenated anacardic acid
  • nanoliposome
  • NTERA-2 cells
  • tumorsphere


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