Nanoparticle drug conjugates

Patent metadata

Field	Value
Publication number	US-2020289668-A1
Application number	US-201916653490-A
Country	US
Kind code	A1
Filing date	Oct 15, 2019
Priority date	May 29, 2014
Publication date	Sep 17, 2020
Grant date	—

Abstract

Described herein are nanoparticle drug conjugates (NDCs), which, in certain embodiments, comprise a non-toxic, multi-modality, clinically proven silica-based nanoparticle platform with covalently attached drug molecules/moieties. The nanoparticle drug conjugates (NDCs) demonstrate imaging capability and targeting ligands which efficiently clear through the kidneys. Furthermore, the conjugates incorporate therapeutic agents for cancer detection, prevention, and/or treatment.

First claim

1 - 19 . (canceled)

20 . A nanoparticle drug conjugate (NDC) comprising:
a nanoparticle having an average diameter from 5 nm to 10 nm that comprises a silica-based core and a silica shell surrounding a least a portion of the core; a linker moiety; a drug moiety; and one or more targeting moieties, wherein the surface of the nanoparticle is covalently modified with polyethylene glycol groups, and wherein the drug moiety and linker moiety form a cleavable linker-drug construct that is covalently linked to the nanoparticle.

21 . The NDC of claim 20 , wherein the linker moiety is enzyme sensitive.

22 . The NDC of claim 21 , wherein the linker moiety is capable of undergoing hydrolysis at the C-terminal end upon protease binding, thereby releasing the drug moiety from the nanoparticle.

23 . The NDC of claim 22 , wherein the protease comprises a serine protease or a cysteine protease.

24 . The NDC of claim 22 , wherein the average drug moiety to nanoparticle ratio ranges from 1 to 20.

25 . The NDC of claim 20 , comprising from 1 to 20 targeting moieties.

26 . The NDC of claim 20 , wherein the targeting moieties bind to receptors on tumor cells.

27 . The NDC of claim 20 , further comprising a fluorescent compound.

28 . The NDC of claim 27 , wherein the fluorescent compound is Cy5.5.

29 . The NDC of claim 20 , wherein the nanoparticle is an organo-silica core shell nanoparticle.

30 . A method of treating of cancer comprising administering a nanoparticle drug conjugate (NDC) comprising:
a nanoparticle having an average diameter from 5 nm to 10 nm that comprises a silica-based core and a silica shell surrounding a least a portion of the core; a linker moiety; a drug moiety; and one or more targeting moieties, wherein the surface of the nanoparticle is covalently modified with polyethylene glycol groups, and wherein the drug moiety and linker moiety form a cleavable linker-drug construct that is covalently linked to the nanoparticle.

Assignees

• Memorial Sloan Kettering Cancer Center
• Univ Cornell

Inventors

• Bradbury Michelle S
• Yoo Barney
• Wiesner Ulrich
• Ma Kai

Classifications

• A61K51/1244

  microparticles or nanoparticles, e.g. polymeric nanoparticles · CPC title

• A61K31/5377

  not condensed and containing further heterocyclic rings, e.g. timolol · CPC title

• A61K47/6923 Primary

  the form being an inorganic particle, e.g. ceramic particles, silica particles, ferrite or synsorb · CPC title

• A61K31/506

  not condensed and containing further heterocyclic rings · CPC title

• A61K47/6935

  the polymer being obtained otherwise than by reactions involving carbon to carbon unsaturated bonds, e.g. polyesters, polyamides or polyglycerol · CPC title