13 research outputs found
Targeting of an antitumor agent, RS-1541 (palmitoyl-rhizoxin), via low-density lipoprotein receptor
Dynamic Pricing for Local Energy Management : Towards a Better Integration of Local Production
Delivery and cytotoxicity of RS-1541 in St-4 human gastric cancer cells in vitro by the low-density-lipoprotein pathway
Drug targeting using low density lipoprotein (LDL): physicochemical factors affecting drug loading into LDL particles
An uncertainty-aware optimization approach for flexible loads of smart grid prosumers: A use case on the Cardiff energy grid
Rerouting lipoprotein nanoparticles to selected alternate receptors for the targeted delivery of cancer diagnostic and therapeutic agents
We report that a lipoprotein-based nanoplatform generated by conjugating tumor-homing molecules to the protein components of naturally occurring lipoproteins reroutes them from their normal lipoprotein receptors to other selected cancer-associated receptors. Multiple copies of these targeting moieties may be attached to the same nanoparticle, or a variety of different targeting moieties can be attached. Such a diverse set of tumor-homing molecules could be used to create a variety of conjugated lipoproteins as multifunctional, biocompatible nanoplatforms with a broad application to both cancer imaging and treatment. The same principle can be applied to imaging and treatment of other diseases and for monitoring specific tissues. To validate this concept, we prepared a low-density lipoprotein (LDL)-based folate receptor (FR)-targeted agent by conjugating folic acid to the Lys residues of the apolipoprotein B (apoB)-100 protein. To demonstrate the ability of the lipoprotein-based nanoplatform to deliver surfaceloaded and core-loaded payloads, the particles were labeled either with the optical reporter 1,1′-dioctadecyl-3,3,3′,3′-tetramethylindocarbocyanine that was intercalated in the phospholipid monolayer or with the lipophilic photodynamic therapy agent, tetra-t-butyl-silicon phthalocyanine bisoleate, that was reconstituted into the lipid core. Cellular localization of the labeled LDL was monitored by confocal microscopy and flow cytometry in FR-overexpressing KB cells, in FR-nonexpressing CHO and HT-1080 cells, and in LDL receptor-overexpressing HepG(2) cells. These studies demonstrate that the folic acid conjugation to the Lys side-chain amino groups blocks binding to the normal LDL receptor and reroutes the resulting conjugate to cancer cells through their FRs