(114a) Engineering Micelles as Multifunctional Nanoparticles for Targeting and Delivery
AIChE Annual Meeting
2009 Annual Meeting
Materials Engineering and Sciences Division
Monday, November 9, 2009 - 12:30pm to 12:55pm
Self-assembled lipid-based micelles can be used to combine targeting, imaging, and therapeutic functions and deliver them efficiently to tumors or other tissues in vivo. The micelles are formed from monomers of functional biomolecules conjugated to lipids, often via a hydrophilic PEG spacer. We have demonstrated that these micelles are useful for in vivo disease targeting and delivery of a therapeutic or imaging payload. Despite their versatility and ease of production, little is known about micelle behavior in vitro or in vivo and what fundamental principles may link their structure and composition to their ability to perform desired therapeutic and diagnostic tasks. In this work, the effect of micelle stability and composition on the behavior of the micelles has been investigated for tumor targeting and therapy. By attaching and varying the length of a hydrophobic tail to the apoptosis inducing peptide, (KLAKLAK)2, the efficacy of the peptide can be increased by up two orders of magnitude. Increasing the length and number of hydrophobic tails was shown to significantly slow micelle break up. Incorporating (KLAKLAK)2 into mixed micelles containing a targeting and internalizing peptide, LyP-1, has also been shown to increase its efficacy in vitro. Current work is aimed at further optimizing how micelle composition, stability, and shape affect the efficacy of therapeutic micelles. In addition to advancing a specific strategy useful for cancer treatment, the insights contained in this work will help provide a blueprint for future design of therapeutic and diagnostic micelles.