Zhang Yifan, Zhang Chenqing, Wu Boda, Li Chunying, Lin Jing, Huang Peng
Marshall Laboratory of Biomedical Engineering, International Cancer Center, Laboratory of Evolutionary Theranostics (LET), School of Biomedical Engineering, Shenzhen University Medical School, Shenzhen 518060, China.
Department of Dermatology and Venereology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, China.
ACS Nano. 2023 Feb 28;17(4):3518-3527. doi: 10.1021/acsnano.2c09893. Epub 2023 Feb 10.
Surgical resection of hepatocellular carcinoma suffers from a high recurrence rate. Ozone directly kills tumor cells by generating reactive oxygen species , but its high reactivity and short half-life severely limit its tumor accumulation and penetration for the treatment of tumors . Herein, a thermoresponsive ozone-enriched spray gel is developed to suppress the tumor recurrence of hepatocellular carcinoma (Huh-7 tumors). Briefly, a perfluorocarbon nanoemulsion (PFTBA@LIP) consisting of a perfluorotributylamine core and a lipid monolayer is fabricated, which is encapsulated in the thermoresponsive hydrogel. Ozone is then dissolved in the nanoemulsion owing to its high affinity to PFTBA (O/PFTBA@LIP@Gel), which effectively improves its stability. Of note is that O/PFTBA@LIP@Gel induces both ferroptosis and apoptosis by regulating the expression of relevant genes (GPX4, ACSL4, CDKN1A, .) and inducing considerable lipid peroxidation, which significantly reduces the tumor recurrence of the Huh-7 tumor by spraying the gel in the surgical cavity and prolongs the survival of tumor-bearing mice.
肝细胞癌的手术切除复发率很高。臭氧通过产生活性氧直接杀死肿瘤细胞，但其高反应性和短半衰期严重限制了其在肿瘤治疗中的肿瘤蓄积和渗透。在此，开发了一种热响应性富臭氧喷雾凝胶以抑制肝细胞癌（Huh-7肿瘤）的肿瘤复发。简而言之，制备了一种由全氟三丁胺核和脂质单层组成的全氟碳纳米乳液（PFTBA@LIP），将其封装在热响应性水凝胶中。由于臭氧与PFTBA具有高亲和力，臭氧随后溶解在纳米乳液中（O/PFTBA@LIP@凝胶），这有效地提高了其稳定性。值得注意的是，O/PFTBA@LIP@凝胶通过调节相关基因（GPX4、ACSL4、CDKN1A等）的表达并诱导大量脂质过氧化来诱导铁死亡和凋亡，通过在手术腔中喷洒凝胶显著降低了Huh-7肿瘤的肿瘤复发率，并延长了荷瘤小鼠的生存期。
