Sep 12, 2007
Nanocarriers for chemotherapy
Liposomal nanocarriers coated with polyethylene glycol have been extensively investigated as chemotherapeutic delivery vehicles particularly due to their prolonged circulation in the bloodstream. Tumor blood vessels are inherently “leaky” allowing for passive accumulation of these long-circulating nanocarriers resulting from increased exposure to the compromised tumor vasculature. The uptake of liposomes by tumor cells (and the inhibition of uptake by non-target cells) is facilitated through the incorporation of targeting ligands on the exterior surface of the nanocarriers. However, in vivo studies utilizing these targeted liposomal nanocarriers often fail to live up to expectations.
Investigators at Georgia Institute of Technology and the University of Texas-Houston Health Science Center have taken a closer look at these targeted nanocarriers and examined the relationships between circulation time, tumor targeting and therapeutic efficacy. In an article published in Nanotechnology the authors demonstrate that the incorporation of targeting ligands can have drastic effects on circulation times of liposomal nanocarriers (due to recognition and clearance by the immune system) thereby decreasing their ability to passively accumulate at the tumor site. Reductions in passive accumulation offset the advantages of targeting resulting in the absence of increased tumor uptake and therapeutic efficacy over comparable non-targeted formulations.
These findings have widespread implications for the design of nanocarrier formulations targeted to tumors, particularly those targeted to tumors with leaky vasculature, which benefit from prolonged circulation in the bloodstream. If the ability to passively accumulate to tumor is compromised by a reduction in circulation time due to targeting ligand incorporation, then targeting will be ineffective and treatment efficacy will be compromised. This report stresses the importance of considering the effects of targeting nanocarriers on circulation time when tailoring these formulations for specific applications.
About the author
Kathleen McNeeley is a doctoral candidate in the Neurological Biomaterials and Therapeutics laboratory in the Department of Biomedical Engineering at Georgia Institute of Technology/Emory University. Co-authors of this work are Ravi Bellamkonda, professor of biomedical engineering at Georgia Institute of Technology/Emory University and Ananth Annapragada, associate professor of Health Information Sciences at the University of Texas-Houston Health Science Center. This work was supported in part by the Georgia Cancer Coalition (to RVB).