Cancer Institute, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, 725 Wanping South Road, Shanghai, 200032, China.
Department of Medical Oncology, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, 725 Wanping South Road, Shanghai, 200032, China.
J Nanobiotechnology. 2021 Oct 15;19(1):323. doi: 10.1186/s12951-021-01063-4.
Knocking down the oncogene ROC1 with siRNA inhibits the proliferation of cancer cells by suppressing the Neddylation pathway. However, methods for delivering siRNA in vivo to induce this high anticancer activity with low potential side effects are urgently needed. Herein, a folic acid (FA)-modified polydopamine (PDA) nanomedicine used in photothermal therapy was designed for siRNA delivery. The designed nanovector can undergo photothermal conversion with good biocompatibility. Importantly, this genetic nanomedicine was selectively delivered to liver cancer cells by FA through receptor-mediated endocytosis. Subsequently, the siRNA cargo was released from the PDA nanomedicine into the tumor microenvironment by controlled release triggered by pH. More importantly, the genetic nanomedicine not only inhibited liver cancer cell proliferation but also promoted liver cell apoptosis by slowing ROC1 activity, suppressing the Neddylation pathway, enabling the accumulation of apototic factor ATF4 and DNA damage factor P-H2AX. Combined with photothermal therapy, this genetic nanomedicine showed superior inhibition of the growth of liver cancer in vitro and in vivo. Taken together, the results indicate that this biodegradable nanomedicine exhibits good target recognition, an effective pH response, application potential for genetic therapy, photothermal imaging and treatment of liver cancer. Therefore, this work contributes to the design of a multifunctional nanoplatform that combines genetic therapy and photothermal therapy for the treatment of liver cancer.
用 siRNA 敲低癌基因 ROC1 通过抑制 Neddylation 通路抑制癌细胞增殖。然而，急需将 siRNA 递送到体内的方法，以诱导这种低潜在副作用的高抗癌活性。在此，设计了一种用于 siRNA 递送的叶酸（FA）修饰的聚多巴胺（PDA）纳米医学。所设计的纳米载体具有良好的生物相容性，可以进行光热转换。重要的是，这种基因纳米医学通过受体介导的内吞作用，通过 FA 选择性递送到肝癌细胞。随后，siRNA 货物通过 pH 触发的控制释放从 PDA 纳米医学中释放到肿瘤微环境中。更重要的是，该基因纳米医学不仅通过减缓 ROC1 活性、抑制 Neddylation 通路来抑制肝癌细胞增殖，还促进肝癌细胞凋亡，从而使凋亡因子 ATF4 和 DNA 损伤因子 P-H2AX 积累。与光热疗法相结合，这种基因纳米医学在体外和体内均表现出对肝癌生长的优异抑制作用。总之，结果表明，这种可生物降解的纳米医学表现出良好的靶向识别、有效的 pH 响应、用于基因治疗的应用潜力、光热成像和治疗肝癌的能力。因此，这项工作有助于设计一种多功能纳米平台，将基因治疗和光热治疗结合起来治疗肝癌。
