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. 2022 Mar 18;20:135. doi: 10.1186/s12967-022-03329-3

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© The Author(s) 2022

Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.

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Fig. 3 — Integration of siRNA and Pro-Pt into uPA peptide-targeted multifunctional shell-core NPs for the synergistic treatment of TNBC. A The tumour-targeted CaP shell-core NPs were prepared using the biomineralization method, where the organic DSPE-PEG-uPA core encapsulates the chemotherapeutic agent Pro-Pt (Pt′) followed by negatively charged siRNA adsorbing in the inorganic porous CaP shell. B The intracellular mechanism of uPA-SP@CaP NPs in TNBC cells. (i) uPA-mediated active tumour targeting increased the intracellular drug concentration. (ii) CaP-mediated lysosomal membrane rupture resulted in lysosomal escape, along with (iii) the release of the BRCA1 siRNA to inhibit the DNA repair pathway. (iv) SiRNA and reduction of Pro-Pt to Pt synergistically induced irreversible DNA damage in TNBC cells. siRNA small interfering RNA, TNBC triple-negative breast cancer

(Reproduced with permission from reference [161]. Copyright 2019, American Chemical Society)