Self-Activating Therapeutic Nanoparticle: A Targeted Tumor Therapy Using Reactive Oxygen Species Self-Generation and Switch-on Drug Release
journal contributionposted on 18.06.2021, 16:03 authored by Rae Hyung Kang, Yumi Kim, Ji Hyeon Kim, Na Hee Kim, Hyun Min Ko, Seung-Hyeon Lee, Inseob Shim, Jong Seung Kim, Hyeung-Jin Jang, Dokyoung Kim
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.
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JStranslational pathwayROS self-generationSelf-Activating Therapeutic Nanopar...nanoformulationCGKRKROS-induced therapysilicon nanoparticlesTargeted Tumor Therapyprecision anticancer treatmentreactive oxygen speciesdrug-induced cell deathReactive Oxygen Species Self-Generationswitch-on drug releaseisothiocyanate-containing chemicalanticancer drugsROS-responsive prodrugcancer cell-specific drug deliverycancer cellpancreatic cancer xenograft mouse modelSNanticancer drugROS-induced cascade nanoparticle de...surface functionalizationSwitch-on Drug ReleaseROS-responsive nanocarriersROS generationcancer-targeting peptideanticancer drug generation