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. 2021 Apr 19;19:111. doi: 10.1186/s12951-021-00854-z

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© The Author(s) 2021

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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Scheme 1 — a Schematic illustration of construction of multi-pocket nanoparticles. b Elucidation of in vivo drug delivery of DOX-loaded MPNs. (i) A large supramolecular structure and PEGylation of MPNs prolong their blood circulation time; (ii) Prolonged circulation facilitates accumulation of large MPNs at tumor sites via the EPR effect; (iii) Shrinkage of MPNs into small-sized nanoparticles in tumor extracellular acidic environment is favourable for deep tumor penetration. (C) Cleavage of disulfide linkages and subsequent disintegration of small nanoparticles in an intracellular reductive environment lead to DOX release into cytoplasm and nucleus