Chondroitin Sulfate-Modified Hydroxyapatite for Caspase-1 Activated Induced Pyroptosis through Ca Overload/ER Stress/STING/IRF3 Pathway in Colorectal Cancer.

Autor: Chen Q; Department of Gastrointestinal Surgery, The First Affiliated Hospital of Jiaxing University, Jiaxing, 314001, China.; The First School of Clinical Medicine, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, China., Peng B; Department of Oncology, Key Laboratory of Biological Targeting Diagnosis, Therapy and Rehabilitation of Guangdong Higher Education Institutes, The Fifth Affiliated Hospital, Guangzhou Medical University, Guangzhou, 510700, China., Lin L; The First School of Clinical Medicine, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, China., Chen J; The First School of Clinical Medicine, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, China., Jiang Z; Department of Oncology, Key Laboratory of Biological Targeting Diagnosis, Therapy and Rehabilitation of Guangdong Higher Education Institutes, The Fifth Affiliated Hospital, Guangzhou Medical University, Guangzhou, 510700, China., Luo Y; Department of Oncology, Key Laboratory of Biological Targeting Diagnosis, Therapy and Rehabilitation of Guangdong Higher Education Institutes, The Fifth Affiliated Hospital, Guangzhou Medical University, Guangzhou, 510700, China., Huang L; Department of Gastrointestinal Surgery, The First Affiliated Hospital of Jiaxing University, Jiaxing, 314001, China., Li J; Department of Gastrointestinal Surgery, The First Affiliated Hospital of Jiaxing University, Jiaxing, 314001, China., Peng Y; Department of Gastrointestinal Surgery, The First Affiliated Hospital of Jiaxing University, Jiaxing, 314001, China., Wu J; Department of Gastrointestinal Surgery, The First Affiliated Hospital of Jiaxing University, Jiaxing, 314001, China., Li W; Department of Breast and Thyroid Surgery, The Second Affiliated Hospital, Hengyang Medical School, University of South China, Hunan, 421000, China., Zhuang K; The First School of Clinical Medicine, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, China., Liang M; Department of Oncology, Key Laboratory of Biological Targeting Diagnosis, Therapy and Rehabilitation of Guangdong Higher Education Institutes, The Fifth Affiliated Hospital, Guangzhou Medical University, Guangzhou, 510700, China.
Jazyk: angličtina
Zdroj: Small (Weinheim an der Bergstrasse, Germany) [Small] 2024 Oct; Vol. 20 (43), pp. e2403201. Date of Electronic Publication: 2024 Jul 17.
DOI: 10.1002/smll.202403201
Abstrakt: Immune checkpoint inhibitors, are the fourth most common therapeutic tool after surgery, chemotherapy, and radiotherapy for colorectal cancer (CRC). However, only a small proportion (≈5%) of CRC patients, those with "hot" (immuno-activated) tumors, benefit from the therapy. Pyroptosis, an innovative form of programmed cell death, is a potentially effective means to mediate a "cold" to "hot" transformation of the tumor microenvironment (TME). Calcium-releasing hydroxyapatite (HAP) nanoparticles (NPs) trigger calcium overload and pyroptosis in tumor cells. However, current limitations of these nanomedicines, such as poor tumor-targeting capabilities and insufficient calcium (Ca) ion release, limit their application. In this study, chondroitin sulfate (CS) is used to target tumors via binding to CD44 receptors and kaempferol (KAE) is used as a Ca homeostasis disruptor to construct CS-HAP@KAE NPs that function as pyroptosis inducers in CRC cells. CS-HAP@KAE NPs bind to the tumor cell membrane, HAP released Ca in response to the acidic environment of the TME, and kaempferol (KAE) enhances the influx of extracellular Ca, resulting in intracellular Ca overload and pyroptosis. This is associated with excessive endoplasmic reticulum stress triggered activation of the stimulator of interferon genes/interferon regulatory factor 3 pathway, ultimately transforming the TME from "cold" to "hot".
(© 2024 The Author(s). Small published by Wiley‐VCH GmbH.)
Databáze: MEDLINE
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