Protocells and their use for targeted delivery of multicomponent cargos to cancer cells

Patent metadata

Field	Value
Publication number	US-9480653-B2
Application number	US-201514627739-A
Country	US
Kind code	B2
Filing date	Feb 20, 2015
Priority date	Oct 21, 2009
Publication date	Nov 1, 2016
Grant date	Nov 1, 2016

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.

First claim

What is claimed is:

1. A method for delivering cargo components to a target cell comprising:
i. providing a protocell compound comprising:
a lipid bilayer encasing a porous particle core,
a plurality types of cargo components disposed within the porous particle core,
a targeting ligand attached to the lipid bilayer for a selective binding to the target cell,
a fusogenic ligand attached to the lipid bilayer, and
a shielding material attached to the lipid bilayer to reduce non-specific binding to the target cell and non-target cells; and

ii. mixing the protocell compound with the target cell such that the protocell compound is selectively bound to the target cell and internalized in the target cell induced by the targeting ligand.

2. The method of claim 1 , wherein one or more cargo components of the plurality types of cargo components are modified with a nuclear localization sequence (NLS) to promote transport of the NLS-modified cargo components through the nuclear pore complex into nucleus of the target cell.

3. The method of claim 1 , further comprising mixing the porous particle core with a solution comprising the plurality of types of cargo components, followed by a liposome fusion process to form the protocell compound.

4. The method of claim 1 , further comprising controlling a size of the porous particle core to attain a balance between a capacity of the plurality types of cargo components and an internalization rate of the protocell compound.

5. The method of claim 1 , further comprising controlling a release rate of intracellular cargo components by incorporating a percentage amount of an amine-containing silane when forming the porous particle core.

6. The method of claim 1 , wherein the lipid bilayer comprises zwitterionic lipids or the lipid bilayer is a hybrid lipid bilayer to increase specific binding of the protocell compound to the target cell.

7. The method of claim 1 , further comprising controlling a dissociation constant (K d ) value of the lipid bilayer by incorporating a combination of a fluid lipid and a non-fluid lipid into the lipid bilayer.

8. The method of claim 1 , wherein the target cell is a cancer cell.

Assignees

• Stc Unm
• Sandia Corp

Inventors

• Brinker C Jeffrey
• Ashley Carlee Erin
• Jiang Xingmao
• Liu Juewen
• Peabody David S
• Wharton Walker Richard
• Carnes Eric
• Chackerian Bryce
• Willman Cheryl L

Classifications

• A61K9/127 Primary

  Synthetic bilayered vehicles, e.g. liposomes or liposomes with cholesterol as the only non-phosphatidyl surfactant · CPC title

• A61K31/704

  attached to a condensed carbocyclic ring system, e.g. sennosides, thiocolchicosides, escin, daunorubicin {(digitoxin A61K31/7048)} · CPC title

• A61K9/1277

  Preparation processes; Proliposomes · CPC title

• A61K31/575

  substituted in position 17 beta by a chain of three or more carbon atoms, e.g. cholane, cholestane, ergosterol, sitosterol · CPC title

• A61K31/513

  having oxo groups directly attached to the heterocyclic ring, e.g. cytosine · CPC title