1. ROS-driven supramolecular nanoparticles exhibiting efficient drug delivery for chemo/Chemodynamic combination therapy for Cancer treatment.
- Author
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Chen, Huikun, Xing, Chengyuan, Lei, Hanqi, Yan, Binyuan, Zhang, Hao, Tong, Tongyu, Guan, Yupeng, Kang, Yang, and Pang, Jun
- Subjects
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PACLITAXEL , *CANCER treatment , *HABER-Weiss reaction , *REACTIVE oxygen species , *NANOPARTICLES , *HYDROXYL group - Abstract
Drug-based supramolecular self-assembling delivery systems have enhanced the bioavailability of chemotherapeutic drugs and reduced systemic side effects; however, improving the delivery efficiency and responsive release ability of these systems remains challenging. This study focuses primarily on the utilization of per-6-thio-β-cyclodextrin (CD) to link a significant quantity of paclitaxel (PTX) via ROS-sensitive thioketal (TK) linkages (designated as CDTP), thereby allowing efficiently drug release when exposed to high levels of reactive oxygen species (ROS) in the tumor microenvironment. To construct these supramolecular nanoparticles (NPs) with CDTP, we introduced PEGylated ferrocene (Fc) through host-guest interactions. The intracellular hydrogen peroxide (H 2 O 2) is converted into hydroxyl radicals (•OH) through the Fc-catalyzed Fenton reaction. Additionally, the generated Fc+ consumes the antioxidant glutathione (GSH). In both in vivo and in vitro experiments, CDTP@Fc-PEG NPs were absorbed effectively by tumor cells, which increased levels of ROS and decreased levels of GSH, disrupting the redox balance of cancer cells and increasing their sensitivity to chemotherapy. Furthermore, CDTP@Fc-PEG NPs exhibited high tumor accumulation and cytotoxicity without causing significant toxicity to healthy organs. Collectively, our results suggest CDTP@Fc-PEG NPs as a promising supramolecular nano-delivery platform for high drug-loading of PTX and synergistic chemotherapy. [Display omitted] • The ROS-driven supramolecular NPs has been constructed successfully and corresponding characterizations have been conducted. • Supramolecular prodrug nano-delivery system that can respond to the TME, while also demonstrating a high drug-loading capacity and delivery efficiency. • The results show that the nanoparticle can deplete GSH and amplify ROS simultaneously, resulting in the disruption of redox homeostasis. And the chemosensitization due to redox imbalance has also verified. • The results of in vitro and in vivo experiments both confirmed the excellent antitumor capability and favorable biosafety of the nanoparticle. [ABSTRACT FROM AUTHOR]
- Published
- 2024
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