An iGlu receptor antagonist and its simultaneous use with an anticancer drug for cancer therapy.
Glutamate receptor antagonists have been known to play a crucial role in the treatment of many neuronal diseases. Recently, these antagonists have also shown therapeutic effects in the treatment of cancer. In this study, an ionotropic glutamate (iGlu) receptor antagonist, 4-hydroxyphenylacetyl spermine (L1), was used concurrently with a common anticancer drug, doxorubicin (Dox), for simultaneous cancer therapy. Mesoporous silica nanoparticles (MSNPs) were employed as the delivery vehicle for both L1 and Dox by conjugating the iGlu receptor antagonist on the surface and encapsulating Dox within the mesopores. Dox was then trapped within the mesopores by functionalizing a redox-cleavable capping group on the MSNP surface, and it could be released upon exposure to the reductive glutathione. In vitro studies on B16F10 and NIH3T3 cell lines revealed that the iGlu receptor antagonist L1 exhibited therapeutic as well as targeting effects. In addition, the simultaneous use of therapeutic L1 and Dox proved to be synergistic in the treatment of cancer. The present work demonstrated the feasibility of employing a delivery system to deliver both neuroprotective drug and anticancer drug for efficient anticancer treatment.
Division of Chemistry and Biological Chemistry, School of Physical and Mathematical Sciences, Nanyang Technological University, 21 Nanyang Link, Singapore 637371 (Singapore) http://www.ntu.edu.sg/home/zhaoyanli/Homepage: http://www.ntu.edu.sg/home/zhaoyanli/
Si Yu
SY
Tan
Chung Yen
CY
Ang
Zhong
Z
Luo
Peizhou
P
Li
Kim Truc
KT
Nguyen
Yanli
Y
Zhao
D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000494:pharmacology*; D045744:Cell Line, Tumor; D004317:Doxorubicin / Q000008:administration & dosage / Q000494:pharmacology*; D004338:Drug Combinations; D016503:Drug Delivery Systems; D004357:Drug Synergism; D006801:Humans; D008545:Melanoma / Q000188:drug therapy*; D051379:Mice; D041681:NIH 3T3 Cells; D053758:Nanoparticles / Q000737:chemistry; D018696:Neuroprotective Agents / Q000008:administration & dosage / Q000494:pharmacology*; D058468:Receptors, Ionotropic Glutamate / Q000037:antagonists & inhibitors*; D012822:Silicon Dioxide / Q000737:chemistry*; D013096:Spermine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology
C000603892:4-hydroxyphenylacetyl spermine; D000970:Antineoplastic Agents; D004338:Drug Combinations; D018696:Neuroprotective Agents; D058468:Receptors, Ionotropic Glutamate; D013096:Spermine; D012822:Silicon Dioxide; D004317:Doxorubicin
antitumor agents; cancer; drug delivery; mesoporous materials; nanoparticles; receptors