Abstract
One of the recent advances in nanotechnology within the medical field is the development of a nanoformulation of anticancer drugs or photosensitizers. Cancer cell-specific drug delivery and upregulation of the endogenous level of reactive oxygen species (ROS) are important in precision anticancer treatment. Within our article, we report a new therapeutic nanoformulation of cancer cell targeting using endogenous ROS self-generation without an external initiator and a switch-on drug release (ROS-induced cascade nanoparticle degradation and anticancer drug generation). We found a substantial cellular ROS generation by treating an isothiocyanate-containing chemical and functionalizing it onto the surface of porous silicon nanoparticles (pSiNPs) that are biodegradable and ROS-responsive nanocarriers. Simultaneously, we loaded an ROS-responsive prodrug (JS-11) that could be converted to the original anticancer drug, SN-38, and conducted further surface functionalization with a cancer-targeting peptide, CGKRK. We demonstrated the feasibility as a cancer-targeting and self-activating therapeutic nanoparticle in a pancreatic cancer xenograft mouse model, and it showed a superior therapeutic efficacy through ROS-induced therapy and drug-induced cell death. The work presented is a new concept of a nanotherapeutic and provides a more feasible clinical translational pathway.
Original language | English |
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Pages (from-to) | 30359-30372 |
Number of pages | 14 |
Journal | ACS Applied Materials and Interfaces |
Volume | 13 |
Issue number | 26 |
DOIs | |
Publication status | Published - 2021 Jul 7 |
Bibliographical note
Funding Information:This research was supported by the Basic Science Research Program through the National Research Foundation (NRF) of Korea (Ministry of Education, NRF-2018-R1A6A1A03025124 and NRF-2018-R1D1A1B07043383, D.K.). This research was also supported by the NRF of Korea (Ministry of Science and ICT, NRF-2019-M3A9H1103783, D.K.); the NRF of Korea (Ministry of Education, Science and Technology, NRF-2017R1A2B4003422, H-J.J.); and the NRF of Korea (CRI project, NRF-2018R1A3B1052702, J.S.K.) and Global Ph.D. fellowship (GPF) program (NRF-2019H1A2A1074096, J.H.K.) funded by the Korean Government.
Publisher Copyright:
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Keywords
- ROS-responsive prodrug
- cancer therapy
- drug-delivery system
- porous silicon nanoparticles
- reactive oxygen species
ASJC Scopus subject areas
- General Materials Science