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. 2023 Jun 8;12:29. doi: 10.1186/s40035-023-00362-0

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© The Author(s) 2023

Open Access This 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. 4 — Mechanisms of action of lysosome-targeting nanoparticles (NPs) and nanocarriers. a Poly(lactic-co-glycolic acid) (PLGA) NPs will dissociate into their respective component acids, lactic acid (pK_a 3.86) and glycolic acid (pK_a 3.83), under mildly acidic conditions and directly acidify lysosomes. b Acidic NPs (AcNPs) formed by poly(ethylene tetrafluorosuccinate-co-succinate) will dissociate into their respective component acids, tetrafluorosuccinic acid (pK_a 1.63) and succinic acid (pK_a 4.20), under mildly acidic conditions and directly acidify lysosomes. c PaNPs are activated upon stimulation by UV light (~ 365 nm), enabling a spatiotemporal control of lysosomal pH by releasing succinic acid. d Acidic nucleolipid nanoemulsions (NL-NEs) are designed to release succinic acid upon enzymatic degradation. Mechanisms of action illustrated are based on the theoretical breakdown of the formed NPs and NL-NEs into their respective component acids. ‘x’ and ‘y’ represent the percentage of each component acid used in the synthesis process. Schematics were created by BioRender and chemical structures were drawn by ChemDraw.