Department of Chemical and Pharmaceutical Engineering, Hefei Normal University, Hefei 230601, China.
School of Biomedical Engineering, Research and Engineering Center of Biomedical Materials, Anhui Medical University, Hefei 230032, China.
Molecules. 2024 Aug 27;29(17):4051. doi: 10.3390/molecules29174051.
Multifunctional targeted drug delivery systems have been explored as a novel cancer treatment strategy to overcome limitations of traditional chemotherapy. The combination of photodynamic therapy and chemotherapy has been shown to enhance efficacy, but the phototoxicity of traditional photosensitizers is a challenge. In this study, we prepared a multi-sensitive composite hydrogel containing gold nanoclusters (Au NCs) and the temperature-sensitive antitumor drug 5-fluorourac il (5-FU) using carboxymethyl cellulose (Carr) as a dual-functional template. Au NCs were synthesized using sodium borohydride as a reducing agent and potassium as a promoter. The resulting Au NCs were embedded in the Carr hydrogel, which was then conjugated with lactobionic acid (LA) as a targeting ligand. The resulting Au NCs/5-FU@Carr-LA composite hydrogel was used for synergistic photodynamic therapy (PDT), photothermal therapy (PTT), and chemotherapy. Au NCs/5-FU@Carr-LA releases the drug faster at pH 5.0 due to the acid sensitivity of the Carr polymer chain. In addition, at 50 °C, the release rate of Au NCs/5-FU@Carr-LA is 78.2%, indicating that the higher temperature generated by the photothermal effect is conducive to the degradation of Carr polymer chains. The Carr hydrogel stabilized the Au NCs and acted as a matrix for drug loading, and the LA ligand facilitated targeted delivery to tumor cells. The composite hydrogel exhibited excellent biocompatibility and synergistic antitumor efficacy, as demonstrated by in vitro and in vivo experiments. In addition, the hydrogel had thermal imaging capabilities, making it a promising multifunctional platform for targeted cancer therapy.
多功能靶向药物递送系统已被探索作为一种新型癌症治疗策略，以克服传统化疗的局限性。光动力疗法和化学疗法的联合已被证明可以提高疗效，但传统光敏剂的光毒性是一个挑战。在这项研究中，我们使用羧甲基纤维素 (Carr) 作为双功能模板，制备了一种含有金纳米簇 (Au NCs) 和温度敏感抗肿瘤药物 5-氟尿嘧啶 (5-FU) 的多敏感复合水凝胶。使用硼氢化钠作为还原剂和钾作为促进剂合成了 Au NCs。所得的 Au NCs 嵌入到 Carr 水凝胶中，然后将其与乳糖酸 (LA) 缀合作为靶向配体。所得的 Au NCs/5-FU@Carr-LA 复合水凝胶用于协同光动力疗法 (PDT)、光热疗法 (PTT) 和化学疗法。由于 Carr 聚合物链的酸敏感性，Au NCs/5-FU@Carr-LA 在 pH 5.0 时更快地释放药物。此外，在 50°C 时，Au NCs/5-FU@Carr-LA 的释放率为 78.2%，表明光热效应产生的较高温度有利于 Carr 聚合物链的降解。Carr 水凝胶稳定了 Au NCs 并充当药物负载的基质，而 LA 配体有利于靶向递送到肿瘤细胞。复合水凝胶表现出优异的生物相容性和协同抗肿瘤功效，这已通过体外和体内实验得到证实。此外，水凝胶具有热成像能力，使其成为一种有前途的多功能靶向癌症治疗平台。
