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Non-equilibrium surfactant partitioning drives self-nanoemulsification for scalable nanocarrier production

Nature Chemical Engineering volume 3, pages 181–192 (2026)Cite this article

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Abstract

Nanocarriers are indispensable in biomedicine, enabling breakthroughs in drug delivery, vaccines and diagnostics. Despite notable successes facilitated by microfluidic technologies, sustainable, low-cost and high-throughput production of monodisperse nanocarriers remains a longstanding challenge. Here we report surfactant-flux-induced interfacial instability, a self-driven nanoemulsification mechanism triggered by non-equilibrium surfactant partitioning at a water–oil interface. This strategy produces 5 l of highly uniform nanoemulsion (0.2 l of disperse phase) in 1 min, producing droplets with diameters as small as 34 nm and polydispersity indices below 0.10. This self-driven nanoemulsification is robust across a broad range of pH values (~3–11) and temperatures (~4–85 °C), demonstrating compatibility with over ten oil–water–surfactant systems and enabling the synthesis of diverse nanocarriers including nanodroplets, micelles, vesicles, polymeric nanoparticles and metal–organic framework nanocrystals. We further demonstrate that surfactant flux underpins the observed interfacial instability, offering a mechanism for nanoemulsification under far-from-equilibrium conditions. This work addresses a bottleneck in nanomanufacturing and provides insights into dynamic surfactant behavior at immiscible interfaces.

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Fig. 1: Schematics of the surfactant-flux-induced self-nanoemulsification.
Fig. 2: Spontaneous surfactant-transfer-induced self-nanoemulsification.
Fig. 3: Driving force in SFIII-based self-nanoemulsification.
Fig. 4: Highly scalable and fast production of nanoemulsions.
Fig. 5: Production of functional nanomaterials.

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Data Availability

Data supporting the findings of this study are available within the Article and its Supplementary Information. Source data are provided with this paper. Source data are also available via figshare at https://doi.org/10.6084/m9.figshare.31154185 (ref. 65).

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Acknowledgements

We acknowledge financial support from the National Natural Science Foundation of China (22278281 (W.W.), 22494712 (L.-Y.C.) and 22278264 (N.-N.D.)), Sichuan Science and Technology Program (2025YFHZ0287 (W.W.) and 2025ZNSFSC0335 (N.-N.D.)), Shanghai Municipal Science and Technology Major Project (N.-N.D.) and Shanghai Pilot Program for Basic Research (N.-N.D.).

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Authors and Affiliations

  1. School of Chemical Engineering, Sichuan University, Chengdu, China

    Qiang Cao  (曹强), Ping Zhang  (张萍), Ting-Yuan Hu  (胡庭瑗), Da-Wei Pan  (潘大伟), Xiao-Jie Ju  (巨晓洁), Zhuang Liu  (刘壮), Rui Xie  (谢锐), Wei Wang  (汪伟) & Liang-Yin Chu  (褚良银)

  2. State Key Laboratory of Synergistic Chem-Bio Synthesis, School of Chemistry and Chemical Engineering, Shanghai Jiao Tong University, Shanghai, China

    Qiang Cao  (曹强), Hong-Yu Yang  (杨虹宇) & Nan-Nan Deng  (邓楠楠)

  3. State Key Laboratory of Advanced Polymer Materials, Sichuan University, Chengdu, China

    Da-Wei Pan  (潘大伟), Xiao-Jie Ju  (巨晓洁), Zhuang Liu  (刘壮), Rui Xie  (谢锐), Wei Wang  (汪伟) & Liang-Yin Chu  (褚良银)

  4. Shanghai Jiao Tong University Sichuan Research Institute, Chengdu, China

    Nan-Nan Deng  (邓楠楠)

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  1. Qiang Cao  (曹强)
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Contributions

Conceptualization, Q.C., N.-N.D. and W.W. Supervision, N.-N.D. and W.W. Methodology, Q.C., P.Z., H.-Y.Y., T.-Y.H., N.-N.D. and W.W. Investigation, Q.C. Visualization, Q.C., P.Z., H.-Y.Y., T.-Y.H., N.-N.D. and W.W. Resources, D.-W.P., X.-J.J., Z.L., R.X., N.-N.D., W.W. and L.-Y.C. Project administration, N.-N.D., W.W. and L.-Y.C. Funding acquisition, N.-N.D., W.W. and L.-Y.C. Writing—original draft, Q.C., N.-N.D. and W.W. Writing—review and editing, N.-N.D. and W.W.

Corresponding authors

Correspondence to Nan-Nan Deng  (邓楠楠) or Wei Wang  (汪伟).

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Competing interests

Sichuan University has filed a Chinese patent application (CN202510294623.2, China, filed on 13 March 2025) based on this work.

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Supplementary information

Supplementary Information (download PDF )

Supplementary Notes 1–11, Figs. 1–33, Tables 1–5 and refs. 1 and 2.

Reporting Summary (download PDF )

Supplementary Video 1 (download MP4 )

Interfacial instability of an LR300-dyed DCM droplet in water with 0.1 wt% of F127.

Supplementary Video 2 (download MP4 )

Interfacial instability of a Cur-dyed DCM droplet in water with 0.1 wt% of RhB-F127.

Supplementary Video 3 (download MP4 )

Self-nanoemulsification process of an LR300-dyed DCM droplet in water with 0.1 wt% of F127.

Supplementary Video 4 (download MP4 )

Fast, manually shaken production of nanoemulsions within 60 s via self-nanoemulsification.

Supplementary Video 5 (download MP4 )

Fast production of 5 l of nanoemulsions within 60 s via self-nanoemulsification.

Supplementary Video 6 (download MP4 )

Fast production of 1 l of PLGA-containing nanoemulsions within 60 s via self-nanoemulsification.

Supplementary Data 1 (download ZIP )

Statistical source data.

Source data

Source Data Fig. 2 (download XLSX )

Statistical source data.

Source Data Fig. 3 (download XLSX )

Statistical source data.

Source Data Fig. 4 (download XLSX )

Statistical source data.

Source Data Fig. 5 (download XLSX )

Statistical source data.

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Cao, Q., Zhang, P., Yang, HY. et al. Non-equilibrium surfactant partitioning drives self-nanoemulsification for scalable nanocarrier production. Nat Chem Eng 3, 181–192 (2026). https://doi.org/10.1038/s44286-026-00367-2

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