Exosome-Mimetic Nanotheranostics for Spatiotemporally Adaptive Sepsis Therapy: A Chemical Orthogonality Design Framework
- 1Division of Trauma Surgery
- 2Department of Plastic and Aesthetic Surgery
- 3Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology
Abstract
Xuan Zhao,1– 4,* Yukun Liu,5,* Yesen Shou,1– 4 Zhikai Xu,1– 4 Xiangjun Bai,1– 4 Fangli Gao,6 Zhanfei Li,1– 4 Yuchang Wang1– 4 1Division of Trauma Surgery, Emergency Surgery & Surgical Critical, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, People’s Republic of China; 2Trauma Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, People’s Republic of China; 3Department of Emergency and Critical Care Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, People’s Republic of China; 4Sino-German Research Institute of Disaster Medicine, Wuhan, 430030, People’s Republic of China; 5Department of Plastic and Aesthetic Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, People’s Republic of China; 6School of Chemistry and Chemical Engineering, Henan Normal University, Xinxiang, People’s Republic of China*These authors contributed equally to this workCorrespondence: Zhanfei Li; Yuchang Wang, Email [email protected]; [email protected]: The host immune status frequently shifts from hyperinflammation toward immunosuppression—although the two states can overlap from onset and vary by tissue compartment and patient—while multiple organs undergo sequential injury. Sepsis progresses along a highly dynamic trajectory. This complexity demands therapeutic platforms that adapt to evolving pathological cues. Exosome-mimetic nanoplatforms combining the biointerfacial properties of exosomes respond independently to specific pathological signals—reactive oxygen species, pH, and dysregulated enzymes. By chemical orthogonality, we mean the independent activation of distinct functional modules by distinct pathological cues without cross-interference. We deconstruct properties of natural exosomes with the chemical tunability of synthetic nanomaterials; this can meet this demand if their design moves beyond structural mimicry toward programmable responsiveness. Here we argue these platforms should be engineered as spatiotemporally programmable systems, with distinct diagnostic and therapeutic functions encoded by chemically orthogonal modules, sepsis pathophysiology translated into actionable chemical design requirements, and examine how membrane engineering, compositional programming, and stimulus-responsive chemistries achieve trajectory-matched sensing, drug release, and immune reprogramming within a single nanosystem, distinguishing systems with uncoupled multi-function execution from simple co-delivery. It should be stated at the outset that no platform described to date fully achieves module independence; the framework therefore defines a design target and research agenda rather than a description of current capabilities. The analysis is based on a systematic screening of PubMed, Web of Science, Embase, and Scopus (2010– 2025), from which the included publications were re-examined against explicit criteria for classifying orthogonal multi-function execution versus co-delivery (Search Strategy and Classification Criteria). We also identify the translational barriers unique to chemically programmable nanotheranostics, including in vivo orthogonality fidelity, manufacturing complexity, and regulatory ambiguity. Applications are re-evaluated through the lens of chemical orthogonality. By connecting the dynamic biology of sepsis with orthogonal chemical design, this review offers guidance for developing exosome-mimetic nanomedicines and a transferable paradigm for other complex diseases.Keywords: sepsis, exosome-mimetic nanoplatforms, spatiotemporal programmability, chemical orthogonality, stimulus-responsive nanotheranostics
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BibTeX
@article{zhao2026exosomemimetic,
title = {{Exosome-Mimetic Nanotheranostics for Spatiotemporally Adaptive Sepsis Therapy: A Chemical Orthogonality Design Framework}},
author = {Zhao X and Liu Y and Shou Y and Xu Z and Bai X and Gao F and Li Z and Wang Y},
journal = {International Journal of Nanomedicine},
year = {2026},
month = nov,
url = {https://www.dovepress.com/exosome-mimetic-nanotheranostics-for-spatiotemporally-adaptive-sepsis--peer-reviewed-fulltext-article-IJN},
note = {CC BY},
}
RIS
TY - JOUR
TI - Exosome-Mimetic Nanotheranostics for Spatiotemporally Adaptive Sepsis Therapy: A Chemical Orthogonality Design Framework
AU - Zhao X
AU - Liu Y
AU - Shou Y
AU - Xu Z
AU - Bai X
AU - Gao F
AU - Li Z
AU - Wang Y
PY - 2026
DA - 2026/11/08
JO - International Journal of Nanomedicine
UR - https://www.dovepress.com/exosome-mimetic-nanotheranostics-for-spatiotemporally-adaptive-sepsis--peer-reviewed-fulltext-article-IJN
AB - Xuan Zhao,1– 4,* Yukun Liu,5,* Yesen Shou,1– 4 Zhikai Xu,1– 4 Xiangjun Bai,1– 4 Fangli Gao,6 Zhanfei Li,1– 4 Yuchang Wang1– 4 1Division of Trauma Surgery, Emergency Surgery & Surgical Critical, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, People’s Republic of China; 2Trauma Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, People’s Republic of China; 3Department of Emergency and Critical Care Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, People’s Republic of China; 4Sino-German Research Institute of Disaster Medicine, Wuhan, 430030, People’s Republic of China; 5Department of Plastic and Aesthetic Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, People’s Republic of China; 6School of Chemistry and Chemical Engineering, Henan Normal University, Xinxiang, People’s Republic of China*These authors contributed equally to this workCorrespondence: Zhanfei Li; Yuchang Wang, Email [email protected]; [email protected]: The host immune status frequently shifts from hyperinflammation toward immunosuppression—although the two states can overlap from onset and vary by tissue compartment and patient—while multiple organs undergo sequential injury. Sepsis progresses along a highly dynamic trajectory. This complexity demands therapeutic platforms that adapt to evolving pathological cues. Exosome-mimetic nanoplatforms combining the biointerfacial properties of exosomes respond independently to specific pathological signals—reactive oxygen species, pH, and dysregulated enzymes. By chemical orthogonality, we mean the independent activation of distinct functional modules by distinct pathological cues without cross-interference. We deconstruct properties of natural exosomes with the chemical tunability of synthetic nanomaterials; this can meet this demand if their design moves beyond structural mimicry toward programmable responsiveness. Here we argue these platforms should be engineered as spatiotemporally programmable systems, with distinct diagnostic and therapeutic functions encoded by chemically orthogonal modules, sepsis pathophysiology translated into actionable chemical design requirements, and examine how membrane engineering, compositional programming, and stimulus-responsive chemistries achieve trajectory-matched sensing, drug release, and immune reprogramming within a single nanosystem, distinguishing systems with uncoupled multi-function execution from simple co-delivery. It should be stated at the outset that no platform described to date fully achieves module independence; the framework therefore defines a design target and research agenda rather than a description of current capabilities. The analysis is based on a systematic screening of PubMed, Web of Science, Embase, and Scopus (2010– 2025), from which the included publications were re-examined against explicit criteria for classifying orthogonal multi-function execution versus co-delivery (Search Strategy and Classification Criteria). We also identify the translational barriers unique to chemically programmable nanotheranostics, including in vivo orthogonality fidelity, manufacturing complexity, and regulatory ambiguity. Applications are re-evaluated through the lens of chemical orthogonality. By connecting the dynamic biology of sepsis with orthogonal chemical design, this review offers guidance for developing exosome-mimetic nanomedicines and a transferable paradigm for other complex diseases.Keywords: sepsis, exosome-mimetic nanoplatforms, spatiotemporal programmability, chemical orthogonality, stimulus-responsive nanotheranostics
SN - 1178-2013
ER -