A Dual-Channel Ca2+ Nanomodulator Induces Intracellular Ca2+ Disorders via Endogenous Ca2+ Redistribution for Tumor Radiosensitization.
Adv Mater
; 36(29): e2401222, 2024 Jul.
Article
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| MEDLINE
| ID: mdl-38690593
ABSTRACT
Tumor cells harness Ca2+ to maintain cellular homeostasis and withstand external stresses from various treatments. Here, a dual-channel Ca2+ nanomodulator (CAP-P-NO) is constructed that can induce irreversible intracellular Ca2+ disorders via the redistribution of tumor-inherent Ca2+ for disrupting cellular homeostasis and thus improving tumor radiosensitivity. Stimulated by tumor-overexpressed acid and glutathione, capsaicin and nitric oxide are successively escaped from CAP-P-NO to activate the transient receptor potential cation channel subfamily V member 1 and the ryanodine receptor for the influx of extracellular Ca2+ and the release of Ca2+ in the endoplasmic reticulum, respectively. The overwhelming level of Ca2+ in tumor cells not only impairs the function of organelles but also induces widespread changes in the gene transcriptome, including the downregulation of a set of radioresistance-associated genes. Combining CAP-P-NO treatment with radiotherapy achieves a significant suppression against both pancreatic and patient-derived hepatic tumors with negligible side effects. Together, the study provides a feasible approach for inducing tumor-specific intracellular Ca2+ overload via endogenous Ca2+ redistribution and demonstrates the great potential of Ca2+ disorder therapy in enhancing the sensitivity for tumor radiotherapy.
Palabras clave
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Calcio
Límite:
Animals
/
Humans
Idioma:
En
Revista:
Adv Mater
/
Adv. mater. (Weinheim Print)
/
Advanced materials (Weinheim Print)
Asunto de la revista:
BIOFISICA
/
QUIMICA
Año:
2024
Tipo del documento:
Article