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Combinatory Cancer Therapeutics with Nanoceria-Capped Mesoporous Silica Nanocarriers through pH-triggered Drug Release and Redox Activity

Singh, Rajendra K., Patel, Kapil D., Mahapatra, Chinmaya, Parthiban, S. Prakash, Kim, Tae-Hyun, Kim, Hae-Won
ACS applied materials & interfaces 2018 v.11 no.1 pp. 288-299
apoptosis, ceric oxide, cytotoxicity, doxorubicin, drug therapy, human cell lines, in vitro studies, nanocarriers, nanomedicine, nanoparticles, neoplasm cells, neoplasms, pH, porous media, reactive oxygen species, silica, synergism
In the field of nanomedicine, drug-loaded nanocarriers that integrate nanotechnology and chemotherapeutics are widely used to achieve synergistic therapeutic effects. Here, we prepared mesoporous silica nanoparticles capped with cerium oxide nanoparticles (COP@MSN) wherein a pH trigger-responsive mechanism was used to control drug release and intracellular drug delivery. We blocked the mesopores of the carboxyl-functionalized MSN with aminated COP. These pores could be opened in acidic conditions to release the loaded drug, thus establishing a pH-responsive drug release system. We loaded doxorubicin (DOX) as anticancer biomolecule into the pores of MSN and capped with COP. The COP@DOX-MSN system showed a typical drug release profile in an acidic medium, which, however, was not observed in a neutral medium. In vitro studies using cancer cell line (HeLa) proved that the COP@DOX-MSN entered efficiently into HeLa cells and released DOX to the level sufficient for cytotoxicity. The cytotoxic effect of COP in cancer cells was facilitated by the pro-oxidant property of COPs, which considerably raised the reactive oxygen species (ROS) level, thereby leading to cellular apoptosis. The combination of DOX with COP (COP@DOX-MSN) showed even higher ROS level, demonstrating a cytotoxic synergism of drug and nanoparticle in terms of ROS generation. Collectively, the COP@DOX-MSN is considered useful for cancer treatment with the combined capacity of pH-controlled drug delivery, chemotherapeutics, and redox activity.