CPC A61K 47/552 (2017.08) [A61K 31/4192 (2013.01); A61K 47/10 (2013.01); A61K 47/545 (2017.08); A61K 47/551 (2017.08); A61K 47/558 (2017.08); A61K 47/60 (2017.08); A61K 47/6923 (2017.08); A61K 47/6929 (2017.08); A61K 49/0032 (2013.01); A61K 49/0093 (2013.01); A61P 35/00 (2018.01)] | 30 Claims |
1. A nanoparticle-drug conjugate (NDC) comprising:
(a) a silica nanoparticle;
(b) polyethylene glycol (PEG) that is covalently bonded to the surface of the silica nanoparticle;
(c) a targeting ligand comprising folic acid, wherein the targeting ligand is attached to the silica nanoparticle through a first spacer group; and
(d) a linker-payload conjugate, wherein:
(i) the payload is exatecan;
(ii) the linker-payload conjugate is attached to the silica nanoparticle through a second spacer group;
(iii) the linker is a protease-cleavable linker; and
(iv) the exatecan is released upon cleavage of the linker,
wherein the first spacer group and the second spacer group each comprise a structure of Formula (NP):
wherein
x is an integer of 0 to 20;
the silicon atom (Si) is a part of the silica nanoparticle; and
the adjacent to the triazole moiety denotes a point of attachment to the targeting ligand or the linker-payload conjugate, either directly or indirectly.
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