Nanoparticle Delivery of 3-Bromopyruvate to Treat Cancer
- *Abstract
-
Application
· Cancer treatment
· Demonstrated in vitro efficacy in prostatecancer cells
ProblemsAddressed (benefits/advantages)
· Can deliver agents to a variety ofmitochondrial compartments (outer mitochondrial membrane, inner mitochondrialmembrane, inter membrane space)
· Targeted delivery of HK2 inhibitors such as3-BP to mitochondria using a gold nanoparticle delivery system, coupled withsubsequent laser irradiation further enhances the therapeutic efficacy of thecomposition
TechnologySummary
A key hallmark of many aggressivecancers is accelerated glucose metabolism. The enzymes that catalyze the first step of glucose metabolism arehexokinases. Hexokinase 2 (HK2) isexpressed at high levels in cancer cells, but only in a limited number ofnormal adult tissues. Cancer cellmitochondrial alterations and metabolic reprogramming using the energy blocker,3-bromopyruvate (3-BP) that inhibits HK could be used in the development oftumor-specific anticancer agents. However, the unique structural and functional characteristics ofmitochondria prohibit selective subcellular targeting of 3-BP to modulate thefunction of this organelle for therapeutic gain.
To help to address thisproblem, Dr. Shanta Dhar developed a mitochondria-targeted gold nanoparticle(T-3-BP-AuNP) decorated with 3-BP and delocalized lipophilictriphenylphosphonium (TPP) cations to target the mitochondrial membranepotential for delivery of 3-BP to cancer cell mitochondria by taking advantageof higher membrane potential in cancer cells compared to normal cells. The construct demonstrated remarkableanticancer activity as well as a markedly enhanced ability to alter cancer cellmetabolism by inhibiting glycolysis as well as demolishing mitochondrialoxidative phosphorylation in prostate cancer cells. Further, this anticancer activity was enhancedupon laser irradiation by exciting the surface plasmon resonance band of AuNP,thereby utilizing a combination of 3-BP chemotherapeutic and AuNP photothermaleffects.
Inventors
· Shanta Dhar, PhD
Dr. Dhar’s research interests lie at the interface ofchemistry and biology with particular emphasis on nanocarrier-mediatedintracellular delivery of payloads for potential applications in variousdiseases.
· Sean Marrache, Graduate student
TechnologyDevelopment and IP Status
· Patentpending in US (Publication WO 2015/138992 A1)
· Discoveryand pre-clinical development stage
- *IP Issue Date
- None
- *IP Type
- Utility
- 國家
- Not Applicable (PCT App)
- 申請號碼
- WO 2015/138992 A1
- 國家/地區
- 美國
