Rational design of multifunctional and smart drug-delivered nanoplatforms is a promising strategy to achieve simultaneous diagnosis, real-time monitoring, and therapy of cancers. Herein, highly uniform and stable selenium nanoparticles with epidermal growth factor receptor (EGFR) targeting and tumor microenvironment-responsive ability (Se-5Fu-Gd-P(Cet/YI-12)) were designed and synthesized by using EGFR as the targeting molecule, gadolinium chelate as the magnetic resonance imaging contrast agent, 5-fluorouracil (5Fu) and cetuximab as drug payloads, polyamidoamine (PAMAM) and 3,3′-dithiobis (sulfosuccinimidyl propionate) as the response agents of intratumoral glutathione, and pH for the treatment and diagnosis of nasopharyngeal carcinoma (NPC). This Se nanoplatform showed excellent magnetic resonance imaging capability and has the potential for its clinical application as a diagnostic agent for tumor tissue specimens. Additionally, in vitro cellular experiments showed that by means of introducing clinical targeted drugs and peptides not only validly increased the intracellular uptake of the Se nanoplatform in NPC cells but also enhanced its penetration ability toward CNE tumor spheroids, resulting in simultaneous inhibition of CNE cell growth, invasion, and migration. In addition, the sequentially triggered bioresponsive property of the nanoplatform in a tumor microenvironment effectively improved the targeting delivery and anticancer efficiency of payloads. Overall, this study not only provides a strategy for facile synthesis of highly uniform and stable nanomedicines and tailing of the bioresponsive property but also sheds light on its application in targeting theranosis of NPC.
Owing to high blood sugar level and chronic inflammation, diabetes tend to cause the overproduction of free radicals in body, which will damage tissue and cells, reduce autoimmunity, and greatly increase the incidence of tumors. Selenium nanoparticles (SeNPs) exhibit high antioxidant activity with anti-tumor ability. In addition, metformin is considered as a clinical drug commonly for the treatment of stage II diabetes. Therefore, in this study, different functionalized SeNPs combined with metformin were performed to detect the feasibility for cancer therapy. The combination of Tween 80 (TW80)-SeNPs and metformin was found to have a synergistic effect on MCF-7 cells. The mechanism of this synergistic effect involved in the induction of DNA damage by affecting the generation of reactive oxygen species through selenoproteins; the upregulation of DNA-damage-related proteins including p-ATM, p-ATR, and p38; the promotion of p21 expression; and the downregulation of cyclin-dependent kinases and cyclin-related proteins causing cell cycle arrest. Furthermore, the expression of AMPK was affected, which in turn to regulate the mitochondrial membrane potential to achieve the synergistic treatment effect.
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