TY - JOUR
T1 - Biological effects of amphiphilic copolymer nanoparticle-encapsulated multi-target chemotherapeutic drugs on MCF-7 human breast cancer cells
AU - Hu, Yili
AU - Zhang, Limin
AU - Wang, Hai
AU - Xu, Shan
AU - Mujeeb, Ayeesha
AU - Nie, Guangjun
AU - Tang, Huiru
AU - Wang, Yulan
N1 - Funding Information:
This work was supported by the grants from the National Natural Science Foundation of China (21675169, 21175149, 91439102 and 21375144) and National Distinguished Young Scientists program (31325010), and the Ministry of Science and Technology 973 (2012CB934004).
Publisher Copyright:
© 2017, Springer Science+Business Media New York.
PY - 2017/5/1
Y1 - 2017/5/1
N2 - Introduction: Amphiphilic copolymer nanoparticle-encapsulated multi-target chemotherapeutic drugs have attracted considerable attention due to their favorable drug efficiency and potential application prospect. Studies have shown that an amphiphilic copolymer, methoxypoly(ethylene glycol)-poly(lactide-co-glycolide) modified with ε-polylysine, and encapsulated with hydrophilic doxorubicin, hydrophobic paclitaxel and survivin siRNA profoundly improved the therapeutic effect both in vitro and in vivo. Objectives: To investigate how MCF-7 cells would response to the exposure of these nanoparticles over with time and assess the biological effects of these nanoparticles and their encapsulated drugs in a holistic manner. Methods: MCF-7 cells were treated with PBS, nanocarrier and three encapsulated drugs, respectively. Metabolic alterations associated with nano-drugs exposure were investigated by performing untargeted NMR metabolomics with combination of targeted fatty acids analysis by GC-MS on cell extracts. Altered metabolic pathways were further validated by qRT-PCR approach. Results: Copolymers showed great biocompatibility with cells as it induced transit metabolic disruptions without affecting cell survival rate. The rapid release of encapsulated doxorubicin resulted in inhibition of glycolysis and DNA synthesis, active proteolysis; these metabolic alternations were recovered after 10 h exposure. However, the combination use of multiple drugs consistently induced cell cycle arrest and apoptosis evidenced by reduction in glycolysis, active proteolysis, stimulated O-GlcNAcylation, reduced the PC:GPC ratio and fatty acids accumulation. Prolonged exposure to encapsulated-multiple-drugs also induced oxidative stress to cells. Conclusion: These findings provide important insight into the biological effects of nanoparticles and their encapsulated drugs while demonstrate that metabolomics is a powerful approach to evaluate the biological effects of nano-drugs.
AB - Introduction: Amphiphilic copolymer nanoparticle-encapsulated multi-target chemotherapeutic drugs have attracted considerable attention due to their favorable drug efficiency and potential application prospect. Studies have shown that an amphiphilic copolymer, methoxypoly(ethylene glycol)-poly(lactide-co-glycolide) modified with ε-polylysine, and encapsulated with hydrophilic doxorubicin, hydrophobic paclitaxel and survivin siRNA profoundly improved the therapeutic effect both in vitro and in vivo. Objectives: To investigate how MCF-7 cells would response to the exposure of these nanoparticles over with time and assess the biological effects of these nanoparticles and their encapsulated drugs in a holistic manner. Methods: MCF-7 cells were treated with PBS, nanocarrier and three encapsulated drugs, respectively. Metabolic alterations associated with nano-drugs exposure were investigated by performing untargeted NMR metabolomics with combination of targeted fatty acids analysis by GC-MS on cell extracts. Altered metabolic pathways were further validated by qRT-PCR approach. Results: Copolymers showed great biocompatibility with cells as it induced transit metabolic disruptions without affecting cell survival rate. The rapid release of encapsulated doxorubicin resulted in inhibition of glycolysis and DNA synthesis, active proteolysis; these metabolic alternations were recovered after 10 h exposure. However, the combination use of multiple drugs consistently induced cell cycle arrest and apoptosis evidenced by reduction in glycolysis, active proteolysis, stimulated O-GlcNAcylation, reduced the PC:GPC ratio and fatty acids accumulation. Prolonged exposure to encapsulated-multiple-drugs also induced oxidative stress to cells. Conclusion: These findings provide important insight into the biological effects of nanoparticles and their encapsulated drugs while demonstrate that metabolomics is a powerful approach to evaluate the biological effects of nano-drugs.
KW - Co-delivery of drugs
KW - Metabolic response
KW - Metabolomics
KW - Nanotechnology
KW - Nuclear magnetic resonance (NMR)
UR - http://www.scopus.com/inward/record.url?scp=85014685096&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85014685096&partnerID=8YFLogxK
U2 - 10.1007/s11306-017-1187-x
DO - 10.1007/s11306-017-1187-x
M3 - Article
AN - SCOPUS:85014685096
SN - 1573-3882
VL - 13
JO - Metabolomics
JF - Metabolomics
IS - 5
M1 - 49
ER -