Campus Units

Materials Science and Engineering, Chemical and Biological Engineering, Ecology, Evolution and Organismal Biology

Document Type

Article

Publication Version

Accepted Manuscript

Publication Date

6-11-2021

Journal or Book Title

Journal of Drug Targeting

DOI

10.1080/1061186X.2021.1941059

Abstract

A library of arginine-like surface modifiers was tested to improve the targetability of DOPE:DOPC liposomes towards myofibroblasts in a tumor microenvironment. Liposomes were characterized using zeta potential and dynamic light scattering. Cell viability remained unchanged for all liposomes. Liposomes were encapsulated using doxorubicin with an encapsulation efficiency >94%. The toxicity of doxorubicin-loaded liposomes was calculated via half-maximal inhibitory concentration (IC50) for fibroblasts and myofibroblasts. These liposomes resulted in significantly lower IC50-values for myofibroblasts compared to fibroblasts, making them more toxic towards the myofibroblasts. Furthermore, a significant increase in cell internalization was observed for myofibroblasts compared to fibroblasts, using fluorescein-loaded liposomes. Most importantly, a novel regression model was constructed to predict the IC50-values for different modifications using their physicochemical properties. Fourteen modifications (A-N) were used to train and validate this model; subsequently, this regression model predicted IC50-values for three new modifications (O, P, and Q) for both fibroblasts and myofibroblasts. Predicted and measured IC50-values showed no significant difference for fibroblasts. For myofibroblasts, modification O showed no significant difference. This study demonstrates that the tested surface modifications can improve targeting to myofibroblasts in the presence of fibroblasts and hence are suitable drug delivery vehicles for myofibroblasts in a tumor microenvironment.

Comments

This is an Accepted Manuscript of an article published by Taylor & Francis in Journal of Drug Targeting on June 11, 2021. Available online at DOI: 10.1080/1061186X.2021.1941059. Posted with permission.

Copyright Owner

Taylor & Francis Group, LLC

Language

en

File Format

application/pdf

Available for download on Saturday, June 11, 2022

Published Version

Share

COinS