A self-sufficient nanoreactor orchestrating calcium overload and sonodynamic/chemodynamic-amplified ferroptosis for oral squamous cell carcinoma therapy.
7 affiliations
- 1Tianjin Key Laboratory on Technologies Enabling Development of Clinical Therapeutics and Diagnostics (Theranostics), School of Pharmacy, The Province and Ministry Co-Sponsored Collaborative Innovation Center for Medical Epigenetics, Tianjin Medical University, Tianjin, 300070, China.
- 2Department of Pharmacy, Shandong Cancer Hospital and Institute, Shandong First Medical University, Shandong Academy of Medical Sciences, Jinan, 250117, P. R. China.
- 3Tianjin Medical University Institute of Stomatology, Tianjin, 300070, People's Republic of China.
- 4Tianjin Key Laboratory on Technologies Enabling Development of Clinical Therapeutics and Diagnostics (Theranostics), School of Pharmacy, The Province and Ministry Co-Sponsored Collaborative Innovation Center for Medical Epigenetics, Tianjin Medical University, Tianjin, 300070, China. [email protected].
- 5Tianjin Key Laboratory on Technologies Enabling Development of Clinical Therapeutics and Diagnostics (Theranostics), School of Pharmacy, The Province and Ministry Co-Sponsored Collaborative Innovation Center for Medical Epigenetics, Tianjin Medical University, Tianjin, 300070, China. [email protected].
- 6Tianjin Key Laboratory on Technologies Enabling Development of Clinical Therapeutics and Diagnostics (Theranostics), School of Pharmacy, The Province and Ministry Co-Sponsored Collaborative Innovation Center for Medical Epigenetics, Tianjin Medical University, Tianjin, 300070, China. [email protected].
- 7Tianjin Medical University Institute of Stomatology, Tianjin, 300070, People's Republic of China. [email protected].
Abstract
Bacteria-derived components hold great promise for cancer therapy owing to their versatile biological properties. We previously reported that Porphyromonas gingivalis cell walls (PgCW), rich in intrinsic µ-oxo bisheme ([Fe(III)PPIX]₂O), can effectively mediate both sonodynamic therapy (SDT) and chemodynamic therapy (CDT). More recently, we identified PgCW's inherent potential to trigger ferroptosis. However, its therapeutic efficacy is limited by the hypoxic tumor microenvironment (TME) and insufficient endogenous hydrogen peroxide (H₂O₂) required for catalytic reactions. Herein, a self-sufficient nanoreactor (DCP) was developed by depositing calcium peroxide (CaO₂) within dendritic large-pore mesoporous silica nanoparticles (DLMSNs), followed by the electrostatic adsorption of PgCW. Under ultrasound irradiation, DCP combines SDT and CDT with continuous glutathione (GSH) depletion to trigger ferroptosis. In the acidic TME, the decomposition of CaO₂ generates O₂ to enhance PgCW-mediated SDT, supplies H₂O₂ for Fenton-like CDT, and releases Ca²⁺ to induce calcium overload. The abundant reactive oxygen species (ROS) from CaO₂-supplemented SDT and CDT, together with GSH exhaustion, amplify ferroptosis, driving severe lipid peroxidation (LPO) and cell membrane rupture to release damage-associated molecular patterns (DAMPs) for primary tumor regression. Furthermore, intracellular calcium overload synergistically promotes this ferroptosis-mediated immunogenic cell death (ICD), which, combined with the innate adjuvanticity of PgCW, drives robust systemic immune activation to suppress distant tumors. In summary, this nanoreactor overcomes TME limitations through self-sufficient substrate supply and efficiently combines calcium overload with amplified ferroptosis to suppress the growth and metastasis of oral squamous cell carcinoma (OSCC). These findings suggest a potential strategy for precision cancer immunotherapy.
Related
- Synergistic nanotheranostic platform for fluorescence/magnetic resonance bimodal imaging-guided near infrared photoimmuno-chemodynamic thermal targeting therapy.
- Volatile organic compounds orchestrating microbiome‐mediated crop resilience: Prospects and challenges for sustainable agriculture
- Annexin 5 is a key player in orchestrating the pollen sequestrome
- LPT: Orchestrating bounded agentic loops for automated protein binder design
- ITLN1 suppresses colorectal cancer progression by orchestrating neutrophil maturation and spatial organization
BibTeX
@article{wu2026selfsufficient,
title = {{A self-sufficient nanoreactor orchestrating calcium overload and sonodynamic/chemodynamic-amplified ferroptosis for oral squamous cell carcinoma therapy.}},
author = {Lei Wu and Chuiyin Wang and Qian Chen and Aiqi Wang and Meiying Peng and Gengming Zhang and Mingxin Cao and Zhaoyang Guo and Xiaoying Yang and Yinsong Wang},
journal = {Journal of nanobiotechnology},
year = {2026},
month = jul,
doi = {10.1186/s12951-026-04783-7},
url = {https://europepmc.org/article/MED/42894188},
note = {CC BY-NC-ND},
}
RIS
TY - JOUR
TI - A self-sufficient nanoreactor orchestrating calcium overload and sonodynamic/chemodynamic-amplified ferroptosis for oral squamous cell carcinoma therapy.
AU - Lei Wu
AU - Chuiyin Wang
AU - Qian Chen
AU - Aiqi Wang
AU - Meiying Peng
AU - Gengming Zhang
AU - Mingxin Cao
AU - Zhaoyang Guo
AU - Xiaoying Yang
AU - Yinsong Wang
PY - 2026
DA - 2026/07/01
JO - Journal of nanobiotechnology
DO - 10.1186/s12951-026-04783-7
UR - https://europepmc.org/article/MED/42894188
AB - Bacteria-derived components hold great promise for cancer therapy owing to their versatile biological properties. We previously reported that Porphyromonas gingivalis cell walls (PgCW), rich in intrinsic µ-oxo bisheme ([Fe(III)PPIX]₂O), can effectively mediate both sonodynamic therapy (SDT) and chemodynamic therapy (CDT). More recently, we identified PgCW's inherent potential to trigger ferroptosis. However, its therapeutic efficacy is limited by the hypoxic tumor microenvironment (TME) and insufficient endogenous hydrogen peroxide (H₂O₂) required for catalytic reactions. Herein, a self-sufficient nanoreactor (DCP) was developed by depositing calcium peroxide (CaO₂) within dendritic large-pore mesoporous silica nanoparticles (DLMSNs), followed by the electrostatic adsorption of PgCW. Under ultrasound irradiation, DCP combines SDT and CDT with continuous glutathione (GSH) depletion to trigger ferroptosis. In the acidic TME, the decomposition of CaO₂ generates O₂ to enhance PgCW-mediated SDT, supplies H₂O₂ for Fenton-like CDT, and releases Ca²⁺ to induce calcium overload. The abundant reactive oxygen species (ROS) from CaO₂-supplemented SDT and CDT, together with GSH exhaustion, amplify ferroptosis, driving severe lipid peroxidation (LPO) and cell membrane rupture to release damage-associated molecular patterns (DAMPs) for primary tumor regression. Furthermore, intracellular calcium overload synergistically promotes this ferroptosis-mediated immunogenic cell death (ICD), which, combined with the innate adjuvanticity of PgCW, drives robust systemic immune activation to suppress distant tumors. In summary, this nanoreactor overcomes TME limitations through self-sufficient substrate supply and efficiently combines calcium overload with amplified ferroptosis to suppress the growth and metastasis of oral squamous cell carcinoma (OSCC). These findings suggest a potential strategy for precision cancer immunotherapy.
SN - 1477-3155
ER -