Precise delivery of therapeutic agents to cell mitochondria for anti-cancer therapy
Described is a targeted molecular scaffold for construction of a metabolic inhibitor loaded with cancer-cell specific activity and anti-tumor immunity. Incorporation of a mitochondria targeting moiety such as triphenylphosphonium cation through a biodegradable linker in allowed for mitochondria targeting of certain metabolic inhibitors like dichloroacetic acid (DCA).
1. A compound having Formula I the following formula:
where
p is from 1 to 3; and
X 3 is a linker
or a pharmaceutically acceptable salt thereof.
2. The compound of claim 1 , wherein the compound is:
or a pharmaceutically acceptable salt thereof.
3. A composition, comprising a compound of claim 1 and a pharmaceutically acceptable carrier.
4. A nanoparticle comprising a hydrophobic core, a hydrophilic outer layer surrounding the core, and a compound of claim 1 .
5. The nanoparticle of claim 4 , wherein the core comprises poly(lactic-co-glycolic) acid.
6. The nanoparticle of claim 4 , wherein the hydrophilic outer layer comprises polyethylene glycol and is attached to the core.
7. The compound of claim 1 , wherein X 3 is CH 2 .
8. The compound of claim 1 , wherein the compound has Formula III