Li Yanxu, Ji Weiben, Wang Chaoying, Chang Lai, Zhang Quan, Gao Jiefeng, Wang Tao, Wu Wei
General Surgery Department, Affiliated Hospital of Yang Zhou University, Medical College of Yang Zhou University, Yang Zhou University, Yang Zhou, Jiang Su 225009, China.
Taixing People's Hospital in Jiangsu Province, Tai Zhou, Jiang Su 225400, China.
ACS Appl Mater Interfaces. 2025 Jan 8;17(1):689-700. doi: 10.1021/acsami.4c18625. Epub 2024 Dec 16.
Electrospun nanocarrier systems, widely employed in the medical field, exhibit the capability to encapsulate multiple drugs and mitigate complications. Doxorubicin hydrochloride (DOX) represents a frequently utilized chemotherapeutic agent for liver cancer patients. Sodium bicarbonate (SB) serves to neutralize the acidic tumor microenvironment, while ibuprofen (IBU) attenuates inflammatory factor production. The combination of these three commonly used drugs facilitates antitumor efficacy and relapse prevention. Composite fibrous membranes were prepared by incorporating the antitumor drug DOX into MSN, which was then codispersed with IBU in a poly l-lactic acid (PLLA) electrospinning solution after acid sensitization using SB. The resulting membrane was characterized using transmission electron microscopy and scanning electron microscopy. The toxic effect of this fibrous membrane and its pro-apoptotic effect on tumor cells were evaluated, along with the expression of cell proliferation-related factors, immune/inflammatory factors, and apoptosis-related factors. Immunohistochemistry and HE staining confirmed its ability to inhibit recurrence of postoperative residual cancer without causing toxicity to vital organs. The PLLA-MSN@DOX-SB-IBU nanofibrous membrane not only mitigates the cardiotoxicity associated with DOX but also inhibits tumor cell proliferation and enhances the tumor microenvironment, demonstrating significant antitumor efficacy. Furthermore, it effectively prevents the recurrence of residual cancer postsurgery while exhibiting excellent biocompatibility. The PLLA-MSN@DOX-SB-IBU nanofibrous membrane demonstrates significant potential in impeding the progression of hepatocellular carcinoma and mitigating the recurrence of residual cancer following surgical intervention for hepatocellular carcinoma.
静电纺丝纳米载体系统在医学领域广泛应用,具有封装多种药物并减轻并发症的能力。盐酸多柔比星(DOX)是肝癌患者常用的化疗药物。碳酸氢钠(SB)用于中和酸性肿瘤微环境,而布洛芬(IBU)可减少炎症因子的产生。这三种常用药物联合使用有助于提高抗肿瘤疗效并预防复发。通过将抗肿瘤药物DOX掺入介孔二氧化硅纳米颗粒(MSN)中制备复合纤维膜,然后在使用SB进行酸敏化后,将其与IBU共分散于聚左旋乳酸(PLLA)静电纺丝溶液中。使用透射电子显微镜和扫描电子显微镜对所得膜进行表征。评估了这种纤维膜的毒性作用及其对肿瘤细胞的促凋亡作用,以及细胞增殖相关因子、免疫/炎症因子和凋亡相关因子的表达。免疫组织化学和苏木精-伊红(HE)染色证实其能够抑制术后残留癌的复发,且不会对重要器官产生毒性。PLLA-MSN@DOX-SB-IBU纳米纤维膜不仅减轻了与DOX相关的心脏毒性,还抑制了肿瘤细胞增殖并改善了肿瘤微环境,显示出显著的抗肿瘤疗效。此外,它有效地预防了术后残留癌的复发,同时表现出优异的生物相容性。PLLA-MSN@DOX-SB-IBU纳米纤维膜在阻碍肝细胞癌进展和减轻肝细胞癌手术干预后残留癌复发方面显示出巨大潜力。