Nanoparticle-based liver-targeting therapy and imaging
A nanoparticle, liver-targeting technology, applied in the directions of organic active ingredients, medical preparations with non-active ingredients, and medical preparations containing active ingredients, etc., can solve the problem of unsatisfactory targeted therapy for primary liver cancer
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Embodiment 1
[0205] Example 1 - Synthesis of Liver-targeted Lactose Long Linker Gold Nanoparticles
[0206] The following describes the preparation and characterization of gold nanoparticles loaded with liver targeting molecules, attachment linkers and carbohydrate diluents attached to the gold surface.
[0207] Ligands LacLL, AL and GlcC2 were used. Hexaethylene glycol undecyl lactoside was chosen as the liver targeting moiety, while the shorter C2 glucoside was used as the diluent moiety. For the attachment of chemotherapeutic payloads or other therapeutic or diagnostic molecules such as drugs, fluorescent dyes and radiotracers, amino functionalized hexaethylene glycol is used. Coupling to the gold core is achieved via gold-sulfur bonds.
[0208] Gold nanoparticles were synthesized with different ratios of the liver-targeting molecule LacLL: LacLL-NP1 (LacLL:AL:GlcC2-9:50:41) and LacLL-NP2 (LacLL:AL:GlcC2-27:50:23).
[0209] For the preparation of the nanoparticles, the ligands LacLL,...
Embodiment 2
[0220] Example 2 - Functionalization of liver targeting lactose long linker gold nanoparticles with different payloads
[0221] Attachment link functionalization and characterization of liver-targeting gold nanoparticles equipped with chemotherapeutics and fluorescent dyes is described below.
[0222] Regarding the functionalization of liver-targeting nanoparticles, two antineoplastic agents were chosen as chemotherapeutic agents: platinum-(IV)-succinate (Pt(IV)-suc) and doxorubicin. Both chemotherapeutics were coupled to the attachment linker via EDC*HCl / NHS facilitated amide conjugation formation. In the case of Pt(IV)-suc, the reaction was performed in DMSO since the compound is not soluble in aqueous systems. Thus, the nanoparticle solution was exchanged for DMSO via lyophilization or centrifuge concentration and subsequent dilution. Next, EDC*HCl / NHS preactivated succinate was reacted with the nanoparticles overnight. A final wash to remove remaining reagents provided ...
Embodiment 3
[0236] Example 3 - Liver targeting of nanoparticles demonstrated in vivo
[0237] The liver-targeting properties of lactose long linker gold nanoparticles may be shown by comparing different nanoparticle constructs in in vivo biodistribution studies. Two lactose long linker nanoparticles (LacLL-NP1(low)+LAcLL-NP2(high)), two similar lactose short linker nanoparticles (LacSL- NP1(low)+LacSL-NP2(high)) (the lactose linked to the C2 linker) and non-targeting nanoparticles (Glc-NP) were injected intravenously into mice, respectively.
[0238] After a 90 minute cycle time, the animals were sacrificed and major organs were harvested and analyzed by ICP-MS to determine the gold concentration in the organs. Mapping of these data provides biodistribution maps for the different constructs ( Figure 6 ). As expected, the liver-targeting constructs were mainly found in the liver, while the non-targeting nanoparticles accumulated in the kidney. It was observed that the linker length of...
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