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. 2020 Sep 25;5:196. doi: 10.1038/s41392-020-00248-x

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© The Author(s) 2020

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 license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license 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 license, visit http://creativecommons.org/licenses/by/4.0/.

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Fig. 6 — In vitro and in vivo antitumor efficacy of NPJ4+Apa by targeting osteosarcoma stem-like/progenitor cells. a IC₅₀ of NP_J4+Apa and free drugs in SJSA-1 or 143B cells. b Morphology (left) and quantitative chart (right) of SJSA-1- or 143B-derived osteosarcoma spheroids treated with PBS, NPs, free drugs, and NP_J4+Apa on day 7, respectively, at J4 concentrations of 5 μM and Apa concentration of 10 μM. c The limiting dilution assay was used to evaluate the self-renewal capacity of SJSA-1 spheroid-derived osteosarcoma stem-like/progenitor cells treated with different formulations. d SJSA-1 spheroid-derived cells (stem-like) were subcutaneously injected into the right hind leg to establish osteosarcoma stem cell-derived xenografted tumors. (left) Representative photographs of the tumors when the nude mice were implanted with SJSA-1 spheroid-derived cells and further treated with different formula for six times. J4 (3 mg/kg), Apa (6 mg/kg), J4 (3 mg/kg) plus Apa (6 mg/kg) group, and NP_J4+Apa (J4, 3 mg/kg; Apa 6 mg/kg) groups. N = 6 in each group. (right) The average tumor volume in each group was measured at a different time point. e Cumulative body weight of mice during treatment. f TUNEL results of the tumor tissues from each treated mice group. Magnification ×200. P values were calculated using Student’s t-test (***P < 0.001, **P < 0.01, or *P < 0.05)