Dataset Information

Tumor-microenvironment activated duplex genome-editing nanoprodrug for sensitized near-infrared titania phototherapy.

ABSTRACT: Near-infrared (NIR)-light-triggered nanomedicine, including photodynamic therapy (PDT) and photothermal therapy (PTT), is growing an attractive approach for cancer therapy due to its high spatiotemporal controllability and minimal invasion, but the tumor eradication is limited by the intrinsic anti-stress response of tumor cells. Herein, we fabricate a tumor-microenvironment responsive CRISPR nanoplatform based on oxygen-deficient titania (TiO_2-x ) for mild NIR-phototherapy. In tumor microenvironment, the overexpressed hyaluronidase (HAase) and glutathione (GSH) can readily destroy hyaluronic acid (HA) and disulfide bond and releases the Cas9/sgRNA from TiO_2-x to target the stress alleviating regulators, i.e., nuclear factor E2-related factor 2 (NRF2) and heat shock protein 90α (HSP90α), thereby reducing the stress tolerance of tumor cells. Under subsequent NIR light illumination, the TiO_2-x demonstrates a higher anticancer effect both in vitro and in vivo. This strategy not only provides a promising modality to kills cancer cells in a minimal side-effects manner by interrupting anti-stress pathways but also proposes a general approach to achieve controllable gene editing in tumor region without unwanted genetic mutation in normal environments.

SUBMITTER: Li Z

PROVIDER: S-EPMC9643290 | biostudies-literature | 2022 Nov

REPOSITORIES: biostudies-literature

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Tumor-microenvironment activated duplex genome-editing nanoprodrug for sensitized near-infrared titania phototherapy.

Li Zekun Z Pan Yongchun Y Du Shiyu S Li Yayao Y Chen Chao C Song Hongxiu H Wu Yueyao Y Luan Xiaowei X Xu Qin Q Guan Xiaoxiang X Song Yujun Y Han Xin X

Acta pharmaceutica Sinica. B 20220702 11

Near-infrared (NIR)-light-triggered nanomedicine, including photodynamic therapy (PDT) and photothermal therapy (PTT), is growing an attractive approach for cancer therapy due to its high spatiotemporal controllability and minimal invasion, but the tumor eradication is limited by the intrinsic anti-stress response of tumor cells. Herein, we fabricate a tumor-microenvironment responsive CRISPR nanoplatform based on oxygen-deficient titania (TiO<sub>2-<i>x</i></sub> ) for mild NIR-phototherapy. In ...[more]

PMID: 36386466

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Project description:Rationale: Fibroblasts, the predominant cell type responsible for tissue fibrosis, are heterogeneous, and the targeting of unique fibrogenic population of fibroblasts is highly expected. Very recently, elevated glycolysis is demonstrated to play a pivotal role in the determination of fibrogenic phenotype of fibroblasts. However, it is lack of specific strategies for targeting and elimination of such fibrogenic populations. In this study, a novel strategy to use the a near-infrared (NIR) dye IR-780 for the targeting and elimination of a fibrogenic population of glycolytic fibroblasts to control the cutaneous scarring is developed. Methods: The identification and cell properties test of fibrogenic fibroblasts with IR-780 were conducted by using fluorescence activated cell sorting, transplantation experiments, in vivo imaging, RNA sequencing in human cell experiments and mouse and rat wound models. The uptake of IR-780 in fibroblasts mediated by HIF-1α/SLCO2A1 and the metabolic properties of IR-780H fibroblasts were investigated using RNA interference or signaling inhibitors. The fibrogenic fibroblast-selective near-infrared phototherapy of IR-780 were evaluated in human cell experiments and mouse wound models. Results: IR-780 is demonstrated to recognize a unique glycolytic fibroblast lineage, which is responsible for the bulk of connective tissue deposition during cutaneous wound healing and cancer stroma formation. Further results identified that SLCO2A1 is involved in the preferential uptake of IR-780 in fibrogenic fibroblasts, which is regulated by HIF-1α. Moreover, with intrinsic dual phototherapeutic activities, IR-780 significantly diminishes cutaneous scarring through the targeted ablation of the fibrogenic population by photothermal and photodynamic effects. Conclusion: This work provides a unique strategy for the targeted control of tissue scarring by fibrogenic fibroblast-selective near-infrared phototherapy. It is proposed that IR-780 based theranostic methodology holds promise for translational medicine aimed at regulation of fibrogenic behavior.

Dataset Information

Tumor-microenvironment activated duplex genome-editing nanoprodrug for sensitized near-infrared titania phototherapy.

Publications

Tumor-microenvironment activated duplex genome-editing nanoprodrug for sensitized near-infrared titania phototherapy.

Similar Datasets

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