Abstract
Here we describe two protocols for the construction of responsive and activable nanomedicines that regulate the tumor microenvironment (TME). The TME is composed of all non-cellular and cellular components surrounding a tumor, including the surrounding blood vessels, immune cells, fibroblasts, signaling molecules, and extracellular matrix and has a crucial role in tumor initiation, growth, and metastasis. Owing to the relatively stable properties of the TME compared to tumor cells, which exhibit frequent genetic mutations and epigenetic changes, therapeutic strategies targeting the TME using multifunctional nanomedicines hold great potential for anti-tumor therapy. By regulating tumor-associated platelets and pancreatic stellate cells (PSCs), the two major players in the TME, we can effectively manipulate the physiological barriers for enhanced drug delivery and significantly improve the tumor penetration and therapeutic efficacy of chemotherapeutics. The preparation and characterization of the multifunctional nanoparticles takes ~10 h for tumor-associated platelet regulation and 16 h for PSC regulation. These nanoformulations can be readily applied to regulate other components in the TME to realize synergistic or additive anti-tumor activity.
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Data availability
The main data discussed in this protocol are available in the supporting primary research papers https://doi.org/10.1038/s41551-017-0115-8 and https://doi.org/10.1038/s41467-018-05906-x. The raw datasets are too large to be publicly shared but are available for research purposes from the corresponding authors upon reasonable request.
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Acknowledgements
This work was supported by the Strategic Priority Research Program of the Chinese Academy of Sciences (XDB36000000), the National Key R&D Program of China (2018YFA0208900 and 2018YFE0205300), the K. C. Wong Education Foundation (GJTD-2018-03), the Key Research Program of Frontier Sciences CAS (ZDBS-LY-SLH039), the National Postdoctoral Program for Innovative Talents (BX20180083), and the National Natural Science Foundation of China (31671023).
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Y.Z. and G.N. originated the method of preparing PLP-D-R; X.H. and G.N. originated the method of preparing Au@PP/RA/siHSP47. All authors wrote the manuscript and approved the contents of the protocol.
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Peer review information Nature Protocols thanks Giuseppe Curigliano, Zhuang Liu and the other, anonymous, reviewer(s) for their contribution to the peer review of this work.
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Key references using this protocol
Li, S. et al. Nat. Biomed. Eng. 1, 667–679 (2017): https://doi.org/10.1038/s41551-017-0115-8
Han, X. et al. Nat. Commun. 9, 3390 (2018): https://doi.org/10.1038/s41467-018-05906-x
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Zhang, Y., Han, X. & Nie, G. Responsive and activable nanomedicines for remodeling the tumor microenvironment. Nat Protoc 16, 405–430 (2021). https://doi.org/10.1038/s41596-020-00421-0
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DOI: https://doi.org/10.1038/s41596-020-00421-0
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