RRC ID 68732
Author Narayana RVL, Jana P, Tomar N, Prabhu V, Nair RM, Manukonda R, Kaliki S, Coupland SE, Alexander J, Kalirai H, Kondapi AK, Vemuganti GK.
Title Carboplatin- and Etoposide-Loaded Lactoferrin Protein Nanoparticles for Targeting Cancer Stem Cells in Retinoblastoma In Vitro.
Journal Invest Ophthalmol Vis Sci
Abstract 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.
Volume 62(14)
Pages 13
Published 2021-11-1
DOI 10.1167/iovs.62.14.13
PII 2778081
PMID 34784412
PMC PMC8606840
MeSH Antineoplastic Agents / pharmacokinetics Antineoplastic Agents / pharmacology Antineoplastic Agents, Phytogenic / pharmacokinetics Antineoplastic Agents, Phytogenic / pharmacology Biological Availability Carboplatin / pharmacokinetics Carboplatin / pharmacology* Chromatography, High Pressure Liquid Culture Media Drug Carriers / chemistry Drug Delivery Systems Etoposide / pharmacokinetics Etoposide / pharmacology* Flow Cytometry Humans Lactoferrin / chemistry* Microscopy, Confocal Microscopy, Electron, Transmission Nanoparticles / chemistry* Neoplastic Stem Cells / drug effects* Neoplastic Stem Cells / metabolism Neoplastic Stem Cells / pathology Retinal Neoplasms / drug therapy* Retinal Neoplasms / metabolism Retinal Neoplasms / pathology Retinoblastoma / drug therapy* Retinoblastoma / metabolism Retinoblastoma / pathology Spectroscopy, Fourier Transform Infrared
IF 3.47
Human and Animal Cells Y79(RCB1645)