Carboplatin- and Etoposide-Loaded Lactoferrin Protein Nanoparticles for Targeting Cancer Stem Cells in Retinoblastoma In Vitro.

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.

• Authors: Revu V L Narayana, Pritikana Jana, Neha Tomar, Varsha Prabhu, Rohini M Nair, Radhika Manukonda, Swathi Kaliki, Sarah E Coupland, Jodi Alexander, Helen Kalirai, Anand K Kondapi, Geeta K Vemuganti
• Journal: Investigative ophthalmology & visual science (Invest Ophthalmol Vis Sci) Vol. 62 Issue 14 Pg. 13 (11 01 2021) ISSN: 1552-5783 [Electronic] United States
• PMID: 34784412 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antineoplastic Agents
• Antineoplastic Agents, Phytogenic
• Culture Media
• Drug Carriers
• Etoposide
• Carboplatin
• Lactoferrin

Topics

• Antineoplastic Agents (pharmacokinetics, pharmacology)
• Antineoplastic Agents, Phytogenic (pharmacokinetics, pharmacology)
• Biological Availability
• Carboplatin (pharmacokinetics, pharmacology)
• Chromatography, High Pressure Liquid
• Culture Media
• Drug Carriers (chemistry)
• Drug Delivery Systems
• Etoposide (pharmacokinetics, pharmacology)
• Flow Cytometry
• Humans
• Lactoferrin (chemistry)
• Microscopy, Confocal
• Microscopy, Electron, Transmission
• Nanoparticles (chemistry)
• Neoplastic Stem Cells (drug effects, metabolism, pathology)
• Retinal Neoplasms (drug therapy, metabolism, pathology)
• Retinoblastoma (drug therapy, metabolism, pathology)
• Spectroscopy, Fourier Transform Infrared