NANOTHERAPY TARGETING RHAMM-POSITIVE TUMORS

摘要

The present technology is directed to nanoparticle compositions and methods useful in treating RHAMM-positive cancers. Such nanoparticle compositions include a plurality of nanoparticles where each nanoparticle includes (i) a particle core with an outer surface; a first layer coating the outer surface of the particle core, the first layer including one or both of poly-L-lysine and poly-L-arginine and optionally including a fluorescent dye; a second layer coating the first layer, the second layer including one or more siRNA that inhibit expression of Bcl-2, inhibit expression of Bcl-xL (BCL2L1), inhibit expression of MCL1, inhibit expression of Bcl-w (BCL2L2), inhibit expression of Bcl-b (BCL2L10), and/or inhibit expression of BFL1 (BCL2A1); a third layer coating the second layer, the third layer including an apoptotic peptide and optionally including a fluorescent dye; and a fourth layer coating the third layer, the fourth layer including hyaluronic acid or a pharmaceutically acceptable salt thereof (HA); and where the plurality of nanoparticles has an intensity- weighted average diameter as determined by dynamic light scattering from about 100 nm to about 300 nm; or (ii) a particle core with an outer surface; a first layer coating the outer surface of the particle core, the first layer including an apoptotic peptide and optionally including a fluorescent dye; a second layer coating the first layer, the second layer including one or more siRNA that inhibit expression of Bcl-2, inhibit expression of Bcl-xL (BCL2L1), inhibit expression of MCL1, inhibit expression of Bcl-w (BCL2L2), inhibit expression of Bcl-b (BCL2L10), and/or inhibit expression of BFL1 (BCL2A1); a third layer coating the second layer, the third layer including one or both of poly-L-lysine and poly-L-arginine and optionally including a fluorescent dye; and a fourth layer coating the third layer, the fourth layer including hyaluronic acid or a pharmaceutically acceptable salt thereof (HA); and where the plurality of nanoparticles has an intensity-weighted average diameter as determined by dynamic light scattering from about 100 nm to about 300 nm.