Membrane lipid coated nanoparticles and method of use
Inventors
Assignees
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Publication Number
US-11471420-B2
Publication Date
2022-10-18
Expiration Date
Abstract
Disclosed is a nanoparticle comprising an inner core comprising a virus; and an outer surface comprising a cellular membrane derived from a cell, and process of making thereof. The virus is an oncolytic virus and cellular membrane is derived from for example red blood cells.
Core Innovation
A nanoparticle is provided that includes an inner core comprising a single oncolytic virus, where the virus is coated with an outer surface comprising a cellular membrane derived from a red blood cell. The nanoparticle outer surface comprises that red blood cell-derived cellular membrane.
The oncolytic virus can be an adenovirus, or can be selected from herpesvirus, vaccinia virus, reovirus, adenovirus, measles virus, parvovirus, or combinations thereof. Red blood cell-derived membranes and membrane-associated immunoprotective markers are discussed, including CD47 and CD59, as well as other membrane-associated markers such as CD55 and CD35 (CR1), including discussion of RBC ghosts and universal donor-type membrane sources.
A critical manufacturing condition is emphasized for enabling coating: mixing and sonication in a non-salt aqueous solution, including sugar solutions such as sucrose and dextrose, rather than saline/PBS or using high-shear methods that are described as failing to produce the intended coating. De-coating experiments, coating thickness estimates, resulting nanoparticle size, and virus detection assay characterization are described as supporting the presence of a coating layer.
The document also discusses intended functional effects of red blood cell membrane coating for circulation, stealth, and delivery, including mechanisms such as EPR.
Claims Coverage
The independent claim family provides coverage for a membrane lipid or cellular membrane-coated nanoparticle where the inner core contains a single oncolytic virus and the outer surface comprises a red blood cell-derived cellular membrane. Across the independent-claim set for this family, the main inventive features are the virus-in-core and red blood cell membrane outer surface, with further refinement including virus identity selection, nanoparticle diameter constraints, and a non-salt sugar-containing condition used with sonication for producing the coating.
A nanoparticle with a single oncolytic virus coated by a red blood cell-derived cellular membrane
A nanoparticle comprising an inner core comprising a single oncolytic virus coated with an outer surface comprising a cellular membrane derived from a red blood cell.
An adenovirus oncolytic virus
The nanoparticle wherein the oncolytic virus is an adenovirus.
A defined set of oncolytic virus selections
The nanoparticle wherein the oncolytic virus is selected from herpesvirus, vaccinia virus, reovirus, adenovirus, measles virus, parvovirus, or combinations thereof.
A nanoparticle diameter range
The nanoparticle wherein the nanoparticle has a diameter ranging from about 110 nm to about 200 nm.
Non-salt sugar solution used during the membrane coating process
The method wherein the red blood cell-derived membrane with depleted internal proteins is mixed with the virus in a non-salt water solution that is a sugar solution.
Sugar concentration range in the non-salt sugar solution
The method wherein the sugar concentration is ranging from about 5% to about 15%.
Interval sonication time
The method wherein interval sonication is performed for about four minutes.
Overall claim coverage centers on a nanoparticle having a single oncolytic virus as the inner core with an outer surface comprising a red blood cell-derived cellular membrane, with refinements that include selecting specific oncolytic viruses, constraining nanoparticle diameter, and using a non-salt sugar-containing solution during sonication to enable formation of the membrane coating.
Stated Advantages
Circulation and stealth are discussed as intended advantages of the red blood cell membrane coating.
Delivery is discussed as an intended advantage, including delivery via mechanisms such as EPR.
Documented Applications
Oncologic and anti-cancer delivery is implied by the use of oncolytic viruses and intended delivery mechanisms, including EPR, together with discussion of immunoprotective markers on red blood cell-derived membranes.
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