Etoposide-loaded layered double hydroxide achieves the best of both worlds: Simultaneous breast carcinoma inhibition and embryo protection via selectively regulating Caspase 3-GSDME pyroptosis pathway

• Published in: Chemical engineering journal (Lausanne, Switzerland : 1996) Switzerland : 1996), 2024-03, Vol.484, p.149485, Article 149485
• Main Authors: Wang, Hong, Yu, Zhiliang, Jing, Guoxin, Wang, Zhaojie, Niu, Jintong, Qian, Yechang, Wang, Shilong
• Format: Article
• Language: English
• Subjects: Cancer during pregnancy; Embryonic development protection; Layered double hydroxide; Oncotherapy; Pyroptosis
• ISSN: 1385-8947; 1873-3212
• DOI: 10.1016/j.cej.2024.149485

[Display omitted] •The first attempt of both tumor inhibition and embryonic protection was manifested.•LDH@VP16 triggered tumor cell pyroptosis while exempted mESC from pyroptosis.•Distribution of VP16 was traced in real time by chemical labeling with BODIPY dye. Cancer incidence within pregnancy is increasing as a trend of “younger” occurrence of tumors and the delayed childbearing in women. However, life-saving oncotherapy for the pregnant mother with tumors poses life-threatening concerns for the developing fetus, highlighting the urgent necessary to explore safe and effective cancer therapeutic agents considering both maternal and neonatal welfare. Our group’s pioneer work has validated that layered double hydroxide (LDH) nanoparticles can serve as a rarely discovered biomaterial for embryo protection. Herein, from a new perspective for simultaneous embryo protection and tumor treatment, we lucubrated the treatment potential of LDH@VP16 fabricated with LDH and etoposide (VP16), and further investigated its possible underlying mechanism accounting for completely opposite effects of LDH@VP16 on tumor cells and mouse embryonic stem cells (mESC). Via labeling VP16 using BODIPY fluorescent dye chemically, we demonstrated that LDH@VP16 with positively charged surface transformed the feature of VP16 located in the nucleus to specifical distribution in mitochondria of tumor cells, but not that of mESC. Through selectively regulating Caspase 3-GSDME pathway, LDH@VP16 remarkably triggered tumor cell pyroptosis while exempted mESC from pyroptosis, which may clarify excellent embryo protection in early embryonic development model. Eventually, for the first time, tumor treatment throughout the gestation period was challenged, and our results firmly manifested the efficiency of LDH@VP16 on tumor inhibition and embryonic development protection simultaneously. Our work may open up a novel viewpoint for the scientific communities on developing antineoplastic agents during pregnancy.