Protocells and their use for targeted delivery of multicomponent cargos to cancer cells
| DWPI Title: Protocell used for targeted delivery of cargo components to cancer cells, comprises porous silica nanoparticle core formed from tetraethylorthosilicate and amine-modified silane precursor, and supported lipid bilayer |
| Abstract: Various embodiments provide materials and methods for synthesizing protocells for use in targeted delivery of cargo components to cancer cells. In one embodiment, the lipid bilayer can be fused to the porous particle core to form a protocell. The lipid bilayer can be modified with targeting ligands or other ligands to achieve targeted delivery of cargo components that are loaded within the protocell to a target cell, e.g., a type of cancer. Shielding materials can be conjugated to the surface of the lipid bilayer to reduce undesired non-specific binding. |
| Use: Protocell used for targeted delivery of cargo components to cancer cells. |
| Advantage: As compared to conventional targeted delivery of therapeutics and diagnostics using liposomes, use of protocells can improve stability and selectivity and can enable the targeted delivery and controlled release of high concentrations of cargo components. Protocells were easily loaded with multicomponent cargo components by simple soaking of the nanoporous core in a solution of the desired cargo(s) prior to liposome fusion. For example, when loaded with a cocktail of doxorubicin, 5-fluorouracil, and cisplatin (a chemotherapeutic drug cocktail known to be particularly effective against hepatocellular carcinoma), as few as one SP94 peptide modified protocell was sufficient to kill a Hep3B cell with induced multiple drug resistance while maintaining 90% hepatocyte viability. In comparison, targeted liposomes could not be loaded with the multicomponent cargo using osmotic gradient or other loading strategies. |
| Novelty: Protocell comprises porous silica nanoparticle core comprising pores, where nanoparticle core is formed from aqueous precursor mixture comprising tetraethylorthosilicate (TEOS) and amine-modified silane precursor; and supported lipid bilayer encasing the porous particle core. The lipid bilayer consists of zwitterionic phospholipid which is 1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC) and/or dipalmitoylphosphatidylcholine (DPPC). The protocell decreases non-specific binding of the protocells when compared to protocells which are encased with lipid bilayer. |
| Filed: 10/21/2010 |
| Application Number: US2010909572A |
| Tech ID: SD 11882.0 |
| This invention was made with Government support under Contract No. DE-NA0003525 awarded by the United States Department of Energy/National Nuclear Security Administration. The Government has certain rights in the invention. |
| Data from Derwent World Patents Index, provided by Clarivate All rights reserved. Republication or redistribution of Clarivate content, including by framing or similar means, is prohibited without the prior written consent of Clarivate. Clarivate and its logo, as well as all other trademarks used herein are trademarks of their respective owners and used under license. |