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Dangosydd eitem ddigidol (DOI)

  • Revu V L Narayana
    University of Hyderabad
  • Pritikana Jana
    University of Hyderabad
  • Neha Tomar
    University of Hyderabad
  • Varsha Prabhu
    University of Hyderabad
  • Rohini M Nair
    University of Hyderabad
  • Radhika Manukonda
    University of Hyderabad
  • Swathi Kaliki
    Prasad Eye Institute, Hyderabad
  • Sarah E Coupland
    Department of Molecular and Clinical Pharmacology, University of Liverpool
  • Jodi Alexander
  • Helen Kalirai
    Department of Molecular and Clinical Pharmacology, University of Liverpool
  • Anand K Kondapi
    University of Hyderabad
  • Geeta K Vemuganti
    University of Hyderabad

Purpose: Cancer stem cells (CSCs) are known to contribute to tumor relapses by virtue of their chemoresistance. With the knowledge that nanoformulations can overcome drug resistance, we evaluated the efficacy and cytotoxicity of clinical-grade carboplatin (CPT)- and etoposide (ETP)-loaded lactoferrin nanoparticles (Lf-Nps) on total, CD133-enriched (non-CSC), and CD133-depleted (CSC) populations of retinoblastoma (Rb) Y79 cells.

Methods: Physicochemical properties of drug-loaded Lf-Nps were measured with transmission electron microscopy and attenuated total reflectance-Fourier transform infrared. The encapsulation efficiency, uptake, and release of drug-loaded Lf-Nps were measured using high-performance liquid chromatography and a UV-visible spectrophotometer. Cytotoxicity of the standard and drug-loaded Lf-Nps was evaluated by the MTT assay.

Results: The mean (SD) size and encapsulation efficiency of Lf-CPT and Lf-ETP were 61.2 (3.94) nm, 60% and 45.15 (5.85) nm, 38%, respectively, and the drug release efficiency was highest at pH 6. The increased drug uptake and lower release of drug-loaded Lf-Nps were observed in CSC and non-CSC populations compared to their standard forms. The relative increase of drug uptake and sustained intracellular retention of the drug-loaded Lf-Nps compared to standard drugs showed an enhanced cytotoxicity up to 50%, especially in Rb Y79 CSCs (IC50: CPT, 230.3; Lf-CPT, 118.2; ETP, 198.1; and Lf-ETP, 129) compared to non-CSCs.

Conclusions: Our study documents an increase in drug uptake, retention, and cytotoxicity of Lf-CPT and Lf-ETP on Y79 CSCs and non-CSCs as compared to their standard drugs in vitro. The reversal of chemoresistance in the CSC population by nanoformulation appears promising with the potential to pave the way for improved targeted therapy and better clinical outcomes.

Iaith wreiddiolSaesneg
Tudalennau (o-i)13
CyfnodolynInvestigative Ophthalmology & Visual Science
Cyfrol62
Rhif y cyfnodolyn14
Dynodwyr Gwrthrych Digidol (DOIs)
StatwsCyhoeddwyd - 16 Tach 2021

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