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

Author:
Singh, Rajendra K., Patel, Kapil D., Mahapatra, Chinmaya, Parthiban, S. Prakash, Kim, Tae-Hyun, Kim, Hae-Won
Source:
ACS applied materials & interfaces 2018 v.11 no.1 pp. 288-299
ISSN:
1944-8252
Subject:
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
Abstract:
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.
Agid:
6270483