Center for Nanoparticle Research, Institute for Basic Science (IBS), Seoul, 08826, Republic of Korea.
School of Chemical and Biological Engineering, and Institute of Chemical Processes, Seoul National University, Seoul, 08826, Republic of Korea.
Adv Mater. 2024 Feb;36(5):e2305394. doi: 10.1002/adma.202305394. Epub 2023 Dec 5.
Lysosomes are critical in modulating the progression and metastasis for various cancers. There is currently an unmet need for lysosomal alkalizers that can selectively and safely alter the pH and inhibit the function of cancer lysosomes. Here an effective, selective, and safe lysosomal alkalizer is reported that can inhibit autophagy and suppress tumors in mice. The lysosomal alkalizer consists of an iron oxide core that generates hydroxyl radicals (•OH) in the presence of excessive H and hydrogen peroxide inside cancer lysosomes and cerium oxide satellites that capture and convert •OH into hydroxide ions. Alkalized lysosomes, which display impaired enzyme activity and autophagy, lead to cancer cell apoptosis. It is shown that the alkalizer effectively inhibits both local and systemic tumor growth and metastasis in mice. This work demonstrates that the intrinsic properties of nanoparticles can be harnessed to build effective lysosomal alkalizers that are both selective and safe.
溶酶体在调节各种癌症的进展和转移中起着关键作用。目前需要开发溶酶体碱化剂，以选择性和安全地改变 pH 值并抑制癌细胞溶酶体的功能。本研究报道了一种有效的、选择性的和安全的溶酶体碱化剂，它可以抑制自噬并抑制小鼠肿瘤。该溶酶体碱化剂由氧化铁核心和氧化铈卫星组成，在癌细胞溶酶体内过量的 H 和过氧化氢存在下，氧化铁核心产生羟基自由基 (•OH)，氧化铈卫星捕获并将 •OH 转化为氢氧根离子。溶酶体碱化导致溶酶体酶活性和自噬受损，从而导致癌细胞凋亡。研究表明，该碱化剂能有效抑制小鼠局部和全身肿瘤的生长和转移。这项工作表明，可以利用纳米粒子的固有特性来构建有效的、选择性的和安全的溶酶体碱化剂。
