RRC ID 44413
Author Kibria G, Hatakeyama H, Ohga N, Hida K, Harashima H.
Title The effect of liposomal size on the targeted delivery of doxorubicin to Integrin αvβ3-expressing tumor endothelial cells.
Journal Biomaterials
Abstract Size of the liposomes (LPs) specially governs its biodistribution. In this study, LPs were developed with controlled sizes, where variation in LP size dictates the ligand-receptor interaction, cellular internalization and its distribution within the tumor microenvironment. The therapeutic efficacies of doxorubicin (DOX)-loaded RGD modified small size (~100 nm in diameter, dnm) and large size (~300 dnm) PEGylated LPs (RGD-PEG-LPs) were compared to that of Doxil (a clinically used DOX-loaded PEG-LP, ~100 dnm) in DOX resistant OSRC-2 (Renal cell carcinoma, RCC) tumor xenografts. Doxil, which accumulated in tumor tissue via the enhanced permeability and retention (EPR) effect, failed to suppress tumor growth. Small size RGD-PEG-LP, that targets the tumor endothelial cells (TECs) and extravasates to tumor cells, failed to provide anti-tumor effect. Large size RGD-PEG-LP preferentially targets the TECs via minimization of the EPR effect, and significantly reduced the tumor growth, which was exerted through its strong anti-angiogenic activity on the tumor vasculature rather than having a direct effect on DOX resistant RCC. The prepared large size RGD-PEG-LP that targets the TECs via interacting with Integrin αvβ3, is a potentially effective and alternate therapeutic strategy for the treatment of DOX resistant tumor cells by utilizing DOX, in cases where Doxil is ineffective.
Volume 34(22)
Pages 5617-27
Published 2013-7
DOI 10.1016/j.biomaterials.2013.03.094
PII S0142-9612(13)00428-6
PMID 23623323
MeSH Animals Antineoplastic Agents / pharmacology Antineoplastic Agents / therapeutic use Cell Death / drug effects Cell Line, Tumor Cell Shape / drug effects Doxorubicin / pharmacology Doxorubicin / therapeutic use* Drug Delivery Systems* Drug Resistance, Neoplasm / drug effects Endocytosis / drug effects Endothelial Cells / drug effects Endothelial Cells / metabolism* Humans Integrin alphaVbeta3 / metabolism* Liposomes / chemistry* Male Mice Mice, Inbred BALB C Neoplasms / blood supply Neoplasms / drug therapy* Neoplasms / metabolism Neoplasms / pathology Oligopeptides / pharmacology Organ Specificity / drug effects Particle Size* Polyethylene Glycols / chemistry Tissue Distribution / drug effects
IF 8.806
Times Cited 32
Human and Animal Cells