NDLI: The energy blocker inside the power house: mitochondria targeted delivery of 3-bromopyruvate† †Electronic supplementary information (ESI) available: Details of materials and instrumentation, additional experimental details, additional figures and tables. See DOI: 10.1039/c4sc01963f Click here for ad

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The energy blocker inside the power house: mitochondria targeted delivery of 3-bromopyruvate† †Electronic supplementary information (ESI) available: Details of materials and instrumentation, additional experimental details, additional figures and tables. See DOI: 10.1039/c4sc01963f Click here for ad

Content Provider	Semantic Scholar
Author	Marrache, Sean Dhar, Shanta
Copyright Year	2015
Abstract	A key hallmark of many aggressive cancers is accelerated glucose metabolism. The enzymes that catalyze the first step of glucose metabolism are hexokinases. High levels of hexokinase 2 (HK2) are found in cancer cells, but only in a limited number of normal tissues. Metabolic reprogramming of cancer cells using the energy blocker, 3-bromopyruvate (3-BP) that inhibits HK2 has the potential to provide tumor-specific anticancer agents. However, the unique structural and functional characteristics of mitochondria prohibit selective subcellular targeting of 3-BP to modulate the function of this organelle for therapeutic gain. A mitochondria targeted gold nanoparticle (T-3-BP-AuNP) decorated with 3-BP and delocalized lipophilic triphenylphosphonium cations to target the mitochondrial membrane potential (Δψm) was developed for delivery of 3-BP to cancer cell mitochondria by taking advantage of higher Δψm in cancer cells compared to normal cells. In vitro studies demonstrated enhanced anticancer activity of T-3-BP-AuNPs compared to the non-targeted construct NT-3-BP-AuNP or free 3-BP. The anticancer activity of T-3-BP-AuNP was further enhanced upon laser irradiation by exciting the surface plasmon resonance band of AuNP and thereby utilizing a combination of 3-BP chemotherapeutic and AuNP photothermal effects. The less toxic behavior of T-3-BPNPs in normal mesenchymal stem cells indicated that these NPs preferentially kill cancer cells. T-3-BP-AuNPs showed enhanced ability to modulate cancer cell metabolism by inhibiting glycolysis as well as demolishing mitochondrial oxidative phosphorylation. Our findings demonstrated that concerted chemo-photothermal treatment of glycolytic cancer cells with a single NP capable of targeting mitochondria mediating simultaneous release of a glycolytic inhibitor and photothermal ablation may have promise as a new anticancer therapy.
Starting Page	1832
Ending Page	1845
Page Count	14
File Format	PDF HTM / HTML
DOI	10.1039/C4SC01963F
Alternate Webpage(s)	http://pubs.rsc.org/en/content/articlepdf/2015/sc/c4sc01963f
Alternate Webpage(s)	http://www.rsc.org/suppdata/sc/c4/c4sc01963f/c4sc01963f1.pdf
Alternate Webpage(s)	https://pubs.rsc.org/en/content/articlepdf/2015/sc/c4sc01963f
Alternate Webpage(s)	https://pubs.rsc.org/en/content/getauthorversionpdf/C4SC01963F
PubMed reference number	25709804
Alternate Webpage(s)	https://doi.org/10.1039/C4SC01963F
Journal	Medline
Volume Number	6
Journal	Chemical science
Language	English
Access Restriction	Open
Content Type	Text
Resource Type	Article

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