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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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.
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.
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.
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 Methods, Figs. 1–26 and Tables 1 and 2.
Spray application of SFH.
Syringe application of SFH.
Spread-fill behaviour of SFH during lung re-inflation-A.
Spread-fill behaviour of SFH during lung re-inflation-B.
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. (2021). https://doi.org/10.1038/s41565-021-00961-w