TY - JOUR
T1 - Overcoming Chemoresistance in Cancer via Combined MicroRNA Therapeutics with Anticancer Drugs Using Multifunctional Magnetic Core-Shell Nanoparticles
AU - Yin, Perry T.
AU - Pongkulapa, Thanapat
AU - Cho, Hyeon Yeol
AU - Han, Jiyou
AU - Pasquale, Nicholas J.
AU - Rabie, Hudifah
AU - Kim, Jong Hoon
AU - Choi, Jeong Woo
AU - Lee, Ki Bum
N1 - Funding Information:
The work was partially supported by the NIH R01 (R01DC016612-01), the NIH R21 (R21AR071101-01), the NSF (CHE-1429062), the ACS (PRF# 55869-ND10), the N.J. Commission on Spinal Cord Research (CSCR16ERG019), and the National Research Foundation of Korea (NRF) [2013K1A4A3055268 and 2016R1A6A1A03012845, funded by the Ministry of Science, ICT and Future Planning (MSIP) and the Ministry of Education of Korea].
Funding Information:
The work was partially supported by the NIH R01 (R01DC016612-01) the NIH R21 (R21AR071101-01), the NSF (CHE-1429062), the ACS (PRF# 55869-ND10),-theN.J. Commission on Spinal Cord-Research-(CSCR16ERG019) and the National Research Foundation of Korea (NRF) [2013K1A4A3055268 and-2016R1A6A1A03012845, funded by the Ministry of Science, ICT and Future Planning (MSIP)-and the Ministry of Education of Korea].
Publisher Copyright:
© 2018 American Chemical Society.
PY - 2018/8/15
Y1 - 2018/8/15
N2 - In this study, we report the use of a multifunctional magnetic core-shell nanoparticle (MCNP), composed of a highly magnetic zinc-doped iron oxide (ZnFe2O4) core nanoparticle and a biocompatible mesoporous silica (mSi) shell, for the simultaneous delivery of let-7a microRNA (miRNA) and anticancer drugs (e.g., doxorubicin) to overcome chemoresistance in breast cancer. Owing to the ability of let-7a to repress DNA repair mechanisms (e.g., BRCA1 and BRCA2) and downregulate drug efflux pumps (e.g., ABCG2), delivery of let-7a could sensitize chemoresistant breast cancer cells (MDA-MB-231) to subsequent doxorubicin chemotherapy both in vitro and in vivo. Moreover, the multifunctionality of our MCNPs allows for the monitoring of in vivo delivery via magnetic resonance imaging. In short, we have developed a multifunctional MCNP-based therapeutic approach to provide an attractive method with which to enhance our ability not only to deliver combined miRNA therapeutics with small-molecule drugs in both selective and effective manner but also to sensitize cancer cells for the enhanced treatment via the combination of miRNA replacement therapy using a single nanoplatform.
AB - In this study, we report the use of a multifunctional magnetic core-shell nanoparticle (MCNP), composed of a highly magnetic zinc-doped iron oxide (ZnFe2O4) core nanoparticle and a biocompatible mesoporous silica (mSi) shell, for the simultaneous delivery of let-7a microRNA (miRNA) and anticancer drugs (e.g., doxorubicin) to overcome chemoresistance in breast cancer. Owing to the ability of let-7a to repress DNA repair mechanisms (e.g., BRCA1 and BRCA2) and downregulate drug efflux pumps (e.g., ABCG2), delivery of let-7a could sensitize chemoresistant breast cancer cells (MDA-MB-231) to subsequent doxorubicin chemotherapy both in vitro and in vivo. Moreover, the multifunctionality of our MCNPs allows for the monitoring of in vivo delivery via magnetic resonance imaging. In short, we have developed a multifunctional MCNP-based therapeutic approach to provide an attractive method with which to enhance our ability not only to deliver combined miRNA therapeutics with small-molecule drugs in both selective and effective manner but also to sensitize cancer cells for the enhanced treatment via the combination of miRNA replacement therapy using a single nanoplatform.
KW - chemoresistance
KW - combination cancer therapy
KW - magnetic core-shell nanoparticles
KW - microRNA therapeutics
KW - targeted delivery
UR - http://www.scopus.com/inward/record.url?scp=85051597488&partnerID=8YFLogxK
U2 - 10.1021/acsami.8b09086
DO - 10.1021/acsami.8b09086
M3 - Article
C2 - 30028120
AN - SCOPUS:85051597488
SN - 1944-8244
VL - 10
SP - 26954
EP - 26963
JO - ACS applied materials & interfaces
JF - ACS applied materials & interfaces
IS - 32
ER -
