Tumor Homing Reactive Oxygen Species Nanoparticle for Enhanced Cancer Therapy
journal contributionposted on 25.06.2019, 03:13 by Hyeon-Yeol Cho, Ahmet Mavi, Sy-Tsong Dean Chueng, Thanapat Pongkulapa, Nicholas Pasquale, Hudifah Rabie, Jiyou Han, Jong Hoon Kim, Tae-Hyung Kim, Jeong-Woo Choi, Ki-Bum Lee
Multifunctional nanoparticles that carry chemotherapeutic agents can be innovative anticancer therapeutic options owing to their tumor-targeting ability and high drug-loading capacity. However, the nonspecific release of toxic DNA-intercalating anticancer drugs from the nanoparticles has significant side effects on healthy cells surrounding the tumors. Herein, we report a tumor homing reactive oxygen species nanoparticle (THoR-NP) platform that is highly effective and selective for ablating malignant tumors. Sodium nitroprusside (SNP) and diethyldithiocarbamate (DDC) were selected as an exogenous reactive oxygen species (ROS) generator and a superoxide dismutase 1 inhibitor, respectively. DDC-loaded THoR-NP, in combination with SNP treatment, eliminated multiple cancer cell lines effectively by the generation of peroxynitrite in the cells (>95% cell death), as compared to control drug treatments of the same concentration of DDC or SNP alone (0% cell death). Moreover, the magnetic core (ZnFe2O4) of the THoR-NP can specifically ablate tumor cells (breast cancer cells) via magnetic hyperthermia, in conjunction with DDC, even in the absence of any exogenous RS supplements. Finally, by incorporating iRGD peptide moieties in the THoR-NP, integrin-enriched cancer cells (malignant tumors, MDA-MB-231) were effectively and selectively killed, as opposed to nonmetastatic tumors (MCF-7), as confirmed in a mouse xenograft model. Hence, our strategy of using nanoparticles embedded with ROS-scavenger-inhibitor with an exogenous ROS supplement is highly selective and effective cancer therapy.
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SNP treatmentcontrol drug treatmentssuperoxide dismutase 1 inhibitorablate tumor cellsexogenous RS supplementsside effectstumor Homing Reactive Oxygen Species Nanoparticledrug-loading capacityMDA-MBexogenous reactive oxygen speciesDDC-loaded THoR-NPintegrin-enriched cancer cellsSodium nitroprussidereactive oxygen species nanoparticleZnFe 2 O 4breast cancer cellsDNA-intercalating anticancer drugstumor-targeting abilitycancer cell linesnonmetastatic tumorsexogenous ROS supplementchemotherapeutic agentsmouse xenograft modeliRGD peptide moietiesMCFEnhanced Cancer Therapy Multifunctional nanoparticlescancer therapy