Abstract
Targeting the hypoxic tumor microenvironment has a broad impact in cancer epigenetics and therapeutics. Oxygen encapsulated nanosize carboxymethyl cellulosic nanobubbles were developed for mitigating the hypoxic regions of tumors to weaken the hypoxia-driven pathways and inhibit tumor growth. We show that 5-methylcytosine (5mC) hypomethylation in hypoxic regions of a tumor can be reverted to enhance cancer treatment by epigenetic regulation, using oxygen nanobubbles in the sub-100 nm size range, both, in vitro and in vivo. Oxygen nanobubbles were effective in significantly delaying tumor progression and improving survival rates in mice models. Further, significant hypermethylation was observed in promoter DNA region of BRCA1 due to oxygen nanobubble (ONB) treatment. The nanobubbles can also reprogram several hypoxia associated and tumor suppressor genes such as MAT2A and PDK-1, in addition to serving as an ultrasound contrast agent. Our approach to develop nanosized oxygen encapsulated bubbles as an ultrasound contrast agent for methylation reversal is expected to have a significant impact in epigenetic programming and to serve as an adjuvant to cancer treatment.
| Original language | English (US) |
|---|---|
| Article number | 9268 |
| Journal | Scientific reports |
| Volume | 7 |
| Issue number | 1 |
| DOIs | |
| State | Published - Dec 1 2017 |
| Externally published | Yes |
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Cite this
Oxygen nanobubbles revert hypoxia by methylation programming. / Bhandari, Pushpak N.; Cui, Yi; Elzey, Bennett D.; Goergen, Craig J.; Long, Christopher M.; Irudayaraj, Joseph.
In: Scientific reports, Vol. 7, No. 1, 9268, 01.12.2017.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Oxygen nanobubbles revert hypoxia by methylation programming
AU - Bhandari, Pushpak N.
AU - Cui, Yi
AU - Elzey, Bennett D.
AU - Goergen, Craig J.
AU - Long, Christopher M.
AU - Irudayaraj, Joseph
PY - 2017/12/1
Y1 - 2017/12/1
N2 - Targeting the hypoxic tumor microenvironment has a broad impact in cancer epigenetics and therapeutics. Oxygen encapsulated nanosize carboxymethyl cellulosic nanobubbles were developed for mitigating the hypoxic regions of tumors to weaken the hypoxia-driven pathways and inhibit tumor growth. We show that 5-methylcytosine (5mC) hypomethylation in hypoxic regions of a tumor can be reverted to enhance cancer treatment by epigenetic regulation, using oxygen nanobubbles in the sub-100 nm size range, both, in vitro and in vivo. Oxygen nanobubbles were effective in significantly delaying tumor progression and improving survival rates in mice models. Further, significant hypermethylation was observed in promoter DNA region of BRCA1 due to oxygen nanobubble (ONB) treatment. The nanobubbles can also reprogram several hypoxia associated and tumor suppressor genes such as MAT2A and PDK-1, in addition to serving as an ultrasound contrast agent. Our approach to develop nanosized oxygen encapsulated bubbles as an ultrasound contrast agent for methylation reversal is expected to have a significant impact in epigenetic programming and to serve as an adjuvant to cancer treatment.
AB - Targeting the hypoxic tumor microenvironment has a broad impact in cancer epigenetics and therapeutics. Oxygen encapsulated nanosize carboxymethyl cellulosic nanobubbles were developed for mitigating the hypoxic regions of tumors to weaken the hypoxia-driven pathways and inhibit tumor growth. We show that 5-methylcytosine (5mC) hypomethylation in hypoxic regions of a tumor can be reverted to enhance cancer treatment by epigenetic regulation, using oxygen nanobubbles in the sub-100 nm size range, both, in vitro and in vivo. Oxygen nanobubbles were effective in significantly delaying tumor progression and improving survival rates in mice models. Further, significant hypermethylation was observed in promoter DNA region of BRCA1 due to oxygen nanobubble (ONB) treatment. The nanobubbles can also reprogram several hypoxia associated and tumor suppressor genes such as MAT2A and PDK-1, in addition to serving as an ultrasound contrast agent. Our approach to develop nanosized oxygen encapsulated bubbles as an ultrasound contrast agent for methylation reversal is expected to have a significant impact in epigenetic programming and to serve as an adjuvant to cancer treatment.
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UR - http://www.scopus.com/inward/citedby.url?scp=85028047984&partnerID=8YFLogxK
U2 - 10.1038/s41598-017-08988-7
DO - 10.1038/s41598-017-08988-7
M3 - Article
C2 - 28839175
AN - SCOPUS:85028047984
VL - 7
JO - Scientific Reports
JF - Scientific Reports
SN - 2045-2322
IS - 1
M1 - 9268
ER -