Department of Chemistry, Izmir Institute of Technology, Urla/Izmir, 35430, Turkiye.
Macromol Biosci. 2024 Oct;24(10):e2400181. doi: 10.1002/mabi.202400181. Epub 2024 Jul 9.
Hypoxia, cancer, tissue damage, and acidic pH conditions are interrelated, as chronic hypoxic conditions enhance the malignant phenotype of cancer cells, causing more aggressive tissue destruction, and hypoxic cells rely on anaerobic glycolysis, leading to the accumulation of lactic acid. Therefore, the administration of oxygen is necessary to support the functions of healthy cells until the formation of new blood vessels and to increase the oxygen supply to cancerous tissues to improve the efficacy of antitumor drugs on tumor cells. In addition to O supply, pH-dependent delivery of anticancer drugs is desired to target cancer cells and reduce drug side effects on healthy cells. However, the simultaneous delivery of O and pH-dependent anticancer drugs via nanomaterials and their effects on the viability of normal and cancer cells under hypoxic conditions have not been studied in sufficient numbers. This study describes the synthesis of a pH-responsive nanomaterial containing oxygen and anticancer drugs that exhibits sustained O release over a 14 d period under hypoxic conditions and pH-dependent sustained release of anticancer drugs over 30 d. The simultaneous administration of O and anticancer drugs results in higher cell survival of normal cells than that of cancer cells under hypoxic and normoxic conditions.
缺氧、癌症、组织损伤和酸性 pH 值条件相互关联，因为慢性缺氧条件会增强癌细胞的恶性表型，导致更具侵袭性的组织破坏，而缺氧细胞依赖于无氧糖酵解，导致乳酸的积累。因此，需要给氧以支持健康细胞的功能，直到新血管形成，并增加对癌组织的氧气供应，以提高肿瘤细胞对抗肿瘤药物的疗效。除了供氧外，还需要 pH 依赖性的抗癌药物输送来靶向癌细胞，并减少对健康细胞的药物副作用。然而，通过纳米材料同时输送 O 和 pH 依赖性抗癌药物及其对缺氧条件下正常和癌细胞活力的影响尚未得到充分研究。本研究描述了一种含有氧气和抗癌药物的 pH 响应性纳米材料的合成，该材料在缺氧条件下能够持续释放氧气长达 14 天，并在 30 天内持续释放 pH 依赖性的抗癌药物。在缺氧和常氧条件下，同时给予 O 和抗癌药物会导致正常细胞的存活率高于癌细胞。
