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Self-assembly of peptide nanocapsules by a solvent concentration gradient

Abstract

Biological systems can create materials with intricate structures and specialized functions. In comparison, precise control of structures in human-made materials has been challenging. Here we report on insect cuticle peptides that spontaneously form nanocapsules through a single-step solvent exchange process, where the concentration gradient resulting from the mixing of water and acetone drives the localization and self-assembly of the peptides into hollow nanocapsules. The underlying driving force is found to be the intrinsic affinity of the peptides for a particular solvent concentration, while the diffusion of water and acetone creates a gradient interface that triggers peptide localization and self-assembly. This gradient-mediated self-assembly offers a transformative pathway towards simple generation of drug delivery systems based on peptide nanocapsules.

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Fig. 1: De novo sequencing and screening of nanocapsule-forming peptides from O. furnacalis.
Fig. 2: The assembly of ICPs in water–acetone mixed solvent.
Fig. 3: Transition of ICP secondary structure during the self-assembly process.
Fig. 4: Exploring the driving forces of ICP self-assembly through MD simulations.
Fig. 5: Encapsulating protein and drug by ICP capsules.
Fig. 6: Intracellular drug, protein and mRNA delivery into cells using ICPs nanocapsules.

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Data availability

The data that support the plots within this paper and other findings of this study are available via DR-NTU at https://doi.org/10.21979/N9/DJV2BM (ref. 58). The data that support the findings of this study are also available from the corresponding authors upon reasonable request. Source data are provided with this paper.

Code availability

All code and scripts used in this study are available from the corresponding authors upon reasonable request.

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Acknowledgements

H.L., X.H. and J.Y acknowledge support from the Singapore National Research Fellowship (NRF-NRFF11-2019-0004) and the Singapore Ministry of Education (MOE) Tier 2 Grant (MOE-T2EP30220-0006). T.L. acknowledges support from the National Natural Science Foundation of China (31871959) and the National Key R&D Program of China (2022YFD1700200). Q.Y. acknowledges support from the National Natural Science Foundation of China (32161133010), the National Key R&D Program of China (2022YFD1700200) and the Shenzhen Science and Technology Program (KQTD20180411143628272). X.Q. and H.G. acknowledge support from the Singapore Ministry of Education (MOE) under its Academic Research Fund Tier 1 award no. RG138/20, no. RG135/22 and a start-up grant from Nanyang Technological University, Singapore and A*STAR, Singapore. G.Z and H.G. acknowledge funding support from the Ministry of Education in Singapore under grant MOE-MOET32022-0002. A.M. acknowledges support from the Singapore Ministry of Education (MOE) through an Academic Research (AcRF) Tier 3 grant (Grant No. MOE 2019-T3-1-012). We acknowledge the Facility for Analysis, Characterisation, Testing and Simulation (FACTS) and NTU Institute of Structural Biology (NISB), Nanyang Technological University, Singapore, for use of their HR-TEM, Cryo-TEM and NMR facilities. Molecular dynamics simulations reported were performed on resources provided by the High Performance Computing Centre at Nanyang Technological University, Singapore, and the National Supercomputing Centre, Singapore (http://www.nscc.sg).

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T.L., Q.Y., H.G. and J.Y. designed the study. Q.Y. conceptualized and supported the study. H.L., H.M., X.H., H.Q., F.Y., T.L. and J.Y. conducted the experiments. H.L. performed the experiment and analysis. X.Q. performed the modelling, simulations and analysis. H.L. and X.Q. collected the data. H.L., X.Q., H.M., X.H., H.Q., G.Z., A.M., Q.Y., T.L., H.G. and J.Y. analysed and interpreted the data. The paper was written through contributions of all authors. All authors have given approval of the final version of the paper for submission.

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Correspondence to Tian Liu, Qing Yang, Huajian Gao or Jing Yu.

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J.Y. and H.L. have filed a Singapore provisional patent application number 10202301815S.

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Li, H., Qian, X., Mohanram, H. et al. Self-assembly of peptide nanocapsules by a solvent concentration gradient. Nat. Nanotechnol. (2024). https://doi.org/10.1038/s41565-024-01654-w

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