It is an urgent need to develop multifunctional agents with integrated accurate diagnostics and treatment for conquering intrinsic limitations of traditional cancer therapies. Herein, a small-size nanocomposite consisting of chlorine e6-integrated gold nanoclusters, hyaluronic acid, doxorubicin and folic acid was synthesized by a simple and mild method. The chlorine e6-integrated gold nanoclusters (Au:Ce6 NCs) were synthesized in an one-step for biological fluorescence imaging and photodynamic therapy. The hyaluronic acid-modified Au:Ce6 (Au:Ce6@HA) can not only act as drug carrier to delivery doxorubicin but increase the cellular selectively target. The folic acid-conjugated Au:Ce6@HA:DOX (Au:Ce6@HA:DOX@FA) was fabricated as a double targeted and pH-responsive drug delivery system for controlling the release of doxorubicin for tumor chemotherapy. The prepared Au:Ce6@HA:DOX@FA nanocomposite possessed small size and high drug encapsulation and loading efficiency. The nanocomposite exhibited good biocompatibility, colloidal stability and potostability, and high cumulative release rate in the acidic microenvironments. The fluorescence microscopy of in vitro confirmed the enhanced cellular uptake of Au:Ce6@HA:DOX@FA for fluorescence imaging. Importantly, the nanocomposite exhibited remarkable mortality of cancer cells under laser irradiation by synergistic chemotherapy and PDT. Together, this study demonstrates the designed small-sized nanocomposite could be used as a promising theranostic agent with dual-responsive tumor targeting capability.

迫切需要开发具有集成准确诊断和治疗功能的多功能药物，以克服传统癌症疗法的内在局限性。在此，通过简单温和的方法合成了由氯 e6 集成的金纳米团簇、透明质酸、阿霉素和叶酸组成的小尺寸纳米复合材料。集成氯 e6 的金纳米团簇 (Au:Ce6 NCs) 是一步合成的，用于生物荧光成像和光动力治疗。透明质酸修饰的 Au:Ce6 (Au:Ce6@HA) 不仅可以作为药物载体递送阿霉素，而且可以增加细胞选择性靶向。叶酸结合的 Au:Ce6@HA:DOX (Au:Ce6@HA:DOX@FA) 被制造为双靶向和 pH 响应的药物递送系统，用于控制肿瘤化疗中阿霉素的释放。所制备的Au:Ce6@HA:DOX@FA纳米复合材料具有体积小、药物包封和负载效率高等特点。该纳米复合材料在酸性微环境中表现出良好的生物相容性、胶体稳定性和钾稳定性，以及高累积释放率。体外荧光显微镜证实了用于荧光成像的 Au:Ce6@HA:DOX@FA 增强的细胞摄取。重要的，该纳米复合材料在协同化疗和 PDT 的激光照射下表现出显着的癌细胞死亡率。总之，这项研究表明设计的小尺寸纳米复合材料可用作具有双重响应肿瘤靶向能力的有前途的治疗诊断剂。