Molecular entrapment in thermophilic ferritin for nanoformulation in photodynamic therapy

• Main Authors: Pasula, Rupali Reddy, Kuniyil, Ambili, Lim, Sierin
• Other Authors: School of Chemical and Biomedical Engineering
• Format: Article
• Language: English
• Published: 2021
• Subjects: Engineering::Chemical engineering; 3D Spheroids; Acridine Orange
• Online Access: https://hdl.handle.net/10356/154636
• Institution: Nanyang Technological University

Nanoformulation of therapeutic and diagnostic agents is beneficial as theyaccumulate at tumor sites due to enhanced permeability and retention effects.However, many in vitro studies performed on 2D cultures lack the realisticdimension of in vivo systems. In this work, a photosensitizer, acridine orange(AO), used in photodynamic therapy of cancer, is nanoformulated byentrapment in thermophilic ferritin. The efficacy is tested on 2D and 3D invitro models and complemented with studies on the cellular uptake routes.Ferritin from the archaeonArchaeoglobus fulgidus(AfFtn) exhibits the uniqueproperty of divalent metal ion or ionic strength mediated assembly, making itan interesting nanocarrier for the entrapment of small molecules. Thephotosensitization and toxicity studies on 2D monolayers and 3D spheroidmodels of colorectal cancer cells show that AO loaded in AfFtn is functional.The killing efficiency in 2D monolayers reaches 50% while the growth of 3Dspheroids is arrested after the first day with a subsequent 10% reduction oftumor diameter over the next 2 days. Results show that AO loaded AfFtn hasbetter penetration ability than free AO alone in 3D spheroid models indicatingthat nanocage formulation provides for an efficient delivery vehicle into thetumor tissue.