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Surface-fill hydrogel attenuates the oncogenic signature of complex anatomical surface cancer in a single application


Tumours growing in a sheet-like manner on the surface of organs and tissues with complex topologies represent a difficult-to-treat clinical scenario. Their complete surgical resection is difficult due to the complicated anatomy of the diseased tissue. Residual cancer often responds poorly to systemic therapy and locoregional treatment is hindered by the limited accessibility to microscopic tumour foci. Here we engineered a peptide-based surface-fill hydrogel (SFH) that can be syringe- or spray-delivered to surface cancers during surgery or used as a primary therapy. Once applied, SFH can shape change in response to alterations in tissue morphology that may occur during surgery. Implanted SFH releases nanoparticles composed of microRNA and intrinsically disordered peptides that enter cancer cells attenuating their oncogenic signature. With a single application, SFH shows efficacy in four preclinical models of mesothelioma, demonstrating the therapeutic impact of the local application of tumour-specific microRNA, which might change the treatment paradigm for mesothelioma and possibly other surface cancers.

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Fig. 1: Application of SFH to complex surface cancer.
Fig. 2: Engineering, physical characterization and transfection efficacy of miRNA nanoparticles.
Fig. 3: Peptide 1–miRNA-215 and peptide 1–miRNA-206 nanoparticles attenuate the oncogenic signature of mesothelioma in vitro.
Fig. 4: Formulation and physical characterization of SFH.
Fig. 5: In vivo delivery and anti-cancer effects of SFH.
Fig. 6: Mesothelioma xenograft models demonstrate therapeutic potential of SFH.

Data availability

The data that support the plots within this paper and other findings of this study are available from the corresponding author upon reasonable request.


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Funding for this study was provided through the intramural programme of the National Cancer Institute, specifically ZIABC011313 (J.P.S.) and ZIABC011657 (C.D.H.). We acknowledge G. Pauly from the Chemical Biology Laboratory, NCI Frederick (NCI-CBL) for help with videography. We thank T. Lizeth López-Silva for help in figure preparation and P. Beard from the NCI-CBL for administrative help. S. Difilippantonio from the Laboratory Animal Sciences Programme at the NCI Frederick is acknowledged for help with animal experiments.

Author information




C.D.H. and J.P.S. conceived the idea of applying hydrogel for delivering microRNA in mesothelioma. J.P.S. and C.D.H. guided the experiments and provided insight into the final interpretation of the results. P.M. conceived the design of SFH, synthesized materials, performed biophysical and cell-based studies and interpreted the results. A.S. performed cell-based studies, in vivo studies and interpreted the results. Z.W., K.D., C.L., N.d.V. and S.T.R.W. helped in biophysical studies. R.P. helped in tumour resection surgeries. J.S. provided cyclic peptide 1. C.A., A.B.J. and B.K. performed histology. N.L.P. performed imaging. P.M. and A.S. analysed all data. P.M., A.S., C.D.H. and J.P.S. co-wrote the manuscript. All authors discussed the results.

Corresponding authors

Correspondence to Chuong D. Hoang or Joel P. Schneider.

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Competing interests

J.P.S., P.M., C.D.H. and A.S. have filed a patent covering this work. All the other authors have no competing interests.

Additional information

Peer review information Nature Nanotechnology thanks Tatiana Segura, Noam Shomron and the other, anonymous, reviewer(s) for their contribution to the peer review of this work.

Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Extended data

Extended Data Fig. 1 Gating strategies used for the analysis of flow cytometry data.

Panel a, gating strategy used for the experiments shown in Fig. 2l and Supplementary Fig. 10a,c; b, gating strategy used for the experiments shown in Supplementary Fig. 11a; c, gating strategy used for the experiments shown in Fig. 2k and Supplementary Fig. 9a; d, gating strategy used for the experiments shown in Supplementary Fig. 9b. In each case, cell only samples were gated first using FSC and SSC parameters to exclude cell debris and large aggregates. The same gating strategy was applied across all samples in the set. This live population was then used for analysis.

Supplementary information

Supplementary Information

Supplementary Methods, Figs. 1–26 and Tables 1 and 2.

Reporting Summary

Supplementary Video 1

Spray application of SFH.

Supplementary Video 2

Syringe application of SFH.

Supplementary Video 3

Spread-fill behaviour of SFH during lung re-inflation-A.

Supplementary Video 4

Spread-fill behaviour of SFH during lung re-inflation-B.

Supplementary Video 5

Spread-fill behaviour of SFH during lung re-inflation-C.

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Majumder, P., Singh, A., Wang, Z. et al. Surface-fill hydrogel attenuates the oncogenic signature of complex anatomical surface cancer in a single application. Nat. Nanotechnol. 16, 1251–1259 (2021).

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