载 cRGD 多肽的 FeO@PDA-DOX 多功能纳米复合材料用于 MRI 及肿瘤化疗-光热治疗

BACKGROUND: Photothermal therapy (PTT) has great potential in the clinical treatment of tumors. However, most photothermal materials are difficult to apply due to their insufficient photothermal conversion efficiencies (PCEs), poor photostabilities and short circulation times. Furthermore, tumor recurrence is likely to occur using PTT only. In the present study, we prepared cyclo (Arg-Gly-Asp-d-Phe-Cys) [c(RGD)] conjugated doxorubicin (DOX)-loaded FeO@polydopamine (PDA) nanoparticles to develop a multifunctional-targeted nanocomplex for integrated tumor diagnosis and treatment. MATERIALS AND METHODS: Cytotoxicity of FeO@PDA-PEG-cRGD-DOX against HCT-116 cells was determined by cck-8 assay. Cellular uptake was measured by confocal laser scanning microscope (CLSM). Pharmacokinetic performance of DOX was evaluated to compare the differences between free DOX and DOX in nanocarrier. Performance in magnetic resonance imaging (MRI) and antitumor activity of complex nanoparticles were evaluated in tumor-bearing nude mice. RESULTS: FeO@PDA-PEG-cRGD-DOX has a particle size of 200-300 nm and a zeta potential of 22.7 mV. Further studies in vitro and in vivo demonstrated their excellent capacity to target tumor cells and promote drug internalization, and significantly higher cytotoxicity with respect to that seen in a control group was shown for the nanoparticles. In addition, they have good thermal stability, photothermal conversion efficiencies (PCEs) and pH responsiveness, releasing more DOX in a mildly acidic environment, which is very conducive to their chemotherapeutic effectiveness in the tumor microenvironment. FeO@PDA-PEG-cRGD-DOX NPs were used in a subcutaneous xenograft tumor model of nude mouse HCT-116 cells showed clear signal contrast in T2-weighted images and effective anti-tumor chemo-photothermal therapy under NIR irradiation. CONCLUSION: According to our results, FeO@PDA-PEG-cRGD-DOX had a satisfactory antitumor effect on colon cancer in nude mice and could be further developed as a potential integrated platform for the diagnosis and treatment of cancer to improve its antitumor activity against colon cancer.

背景：光热疗法（PTT）在肿瘤的临床治疗中有很大的潜力。然而，由于光热转换效率（PCE）不足、光稳定性差和循环时间短，大多数光热材料难以应用。此外，仅使用 PTT 可能会导致肿瘤复发。在本研究中，我们制备了环（精氨酸-甘氨酸-天冬氨酸-苯丙氨酸-半胱氨酸）[c（RGD）]偶联阿霉素（DOX）负载的 FeO@聚多巴胺（PDA）纳米粒子，以开发一种多功能靶向纳米复合物，用于肿瘤的综合诊断和治疗。

材料和方法：通过 cck-8 测定法测定 FeO@PDA-PEG-cRGD-DOX 对 HCT-116 细胞的细胞毒性。通过共聚焦激光扫描显微镜（CLSM）测量细胞摄取。通过评估 DOX 的药代动力学性能来比较游离 DOX 和纳米载体中 DOX 的差异。在荷瘤裸鼠中评估磁共振成像（MRI）和复合纳米粒子的抗肿瘤活性。

结果：FeO@PDA-PEG-cRGD-DOX 的粒径为 200-300nm，zeta 电位为 22.7mV。进一步的体外和体内研究表明，它们具有优异的靶向肿瘤细胞和促进药物内化的能力，与对照组相比，纳米粒子的细胞毒性显著提高。此外，它们具有良好的热稳定性、光热转换效率（PCE）和 pH 响应性，在微酸性环境中释放更多的 DOX，这非常有利于其在肿瘤微环境中的化学治疗效果。FeO@PDA-PEG-cRGD-DOX NPs 用于裸鼠 HCT-116 细胞的皮下异种移植肿瘤模型，在 T2 加权图像中显示出清晰的信号对比，并在近红外照射下进行有效的抗肿瘤化疗-光热治疗。

结论：根据我们的结果，FeO@PDA-PEG-cRGD-DOX 对裸鼠结肠癌具有令人满意的抗肿瘤作用，可进一步开发为癌症诊断和治疗的潜在综合平台，以提高其对结肠癌的抗肿瘤活性。