(56d) Peptide Modified Liposomes for Treatment of Multiple Myeloma Via Selective Targeting of CD138 and Dual Targeting of CD138 and VLA-4

Liposomal drug delivery methods for cancer treatment have increasingly been used successfully to improve patient outcome and decrease systemic toxicity. The next step to further improve this method is the addition of targeting elements to the surface of the liposome delivery vehicle, increasing cellular uptake of the nanoparticle and the drug load it carries. Making use of multivalency effects associated with the overexpression of a receptor unique to the target cancer type allows this increased uptake to selectively target cancerous cells and overcome drug resistance. We analyzed the effects of a CD138 targeting peptide, AG73, used as an active targeting element for liposomal delivery in vitro. CD138 is overexpressed in 95% of multiple myeloma cases, making it a good choice for targeting. Various parameters tested include the length of an EG peptide-linker, liposome diameter, targeting peptide surface density, and the length of an oligolysine chain to increase peptide hydrophilicity. Liposomes targeted with AG73 showed significantly increased cellular uptake over that of non-targeted liposomes, from up to 7-fold at surface densities as low as 0.1% to up to 50-fold at surface densities of 1%. We also analyzed dual targeting of CD138 and another receptor, VLA-4. VLA-4 is also commonly overexpressed in multiple myeloma, and a targeted peptide has previously been discovered and analyzed in liposomal studies. Various ratios of VLA-4 and CD138 on the same liposomes were used to determine the most optimal ratio. Surface densities of 0.1% for CD138 and 0.25% or 0.5% for VLA-4 with a peptide-linker of EG6 were determined to lead the greatest increase in cellular uptake. This dual targeting of two commonly overexpressed receptors could lead to increased efficacy and reduced toxicity in liposomal cancer treatments by selectively targeting only the cancerous cells and leaving healthy cells unharmed.