癌症是世界范围内的重大公共卫生问题，是世界人类第二大死因。本研究旨在制备负载甲氨蝶呤的表面修饰固体脂质纳米粒子（SLN），以潜在用作癌症治疗的化疗制剂。衍生自肉豆蔻酸 (C14H30O2) 和对乙酰氨基酚 (AAP) 的脂质 (C14-AAP) 被用作过度表达环氧合酶 2 (COX-2) 酶的人乳腺癌和肺癌细胞的靶向配体。采用动态光散射（DLS）、差示扫描量热法（DSC）、粉末X射线衍射（PXRD）、紫外-可见（UV-vis）光谱等多种方法对由硬脂酸和C14-AAP组成的SLN进行了表征。高分辨率透射电子显微镜（HRTEM）和场发射扫描电子显微镜（FESEM）技术。通过在人乳腺癌 (MCF7) 和人肺癌细胞系 (A549) 中进行 MTT 测定和流式细胞术研究来进行体外细胞毒性研究。通过逆转录聚合酶链反应（RT-PCR）检测MCF7和A549细胞系中COX-2酶的表达水平。在两种细胞系中均观察到高水平的 COX-2 表达。在 MC7 和 A549 细胞系中进行的体外细胞毒性研究表明，在 MTT、流式细胞术、克隆形成试验和细胞分析中，表面修饰的负载甲氨蝶呤的 SLN 在两种细胞系中比游离甲氨蝶呤更有效地杀死细胞和诱导细胞凋亡。蛋白质印迹研究。表面修饰的 SLN 采用 99mTc 进行放射性标记，%RCP 大于 95%。 99mTc 标记的 SLN 在携带黑色素瘤肿瘤的 C57BL6 小鼠中的体内生物分布研究表明，注射后 3 小时，肿瘤对放射性示踪剂有中等程度的摄取。 SPECT/CT 图像与生物分布结果一致。这项研究表明，AAP 修饰的 SLN 可能成为癌症治疗的潜在化疗制剂。

Cancer is a major public health problem worldwide, and it is the second leading cause of death of humans in the world. The present study has been directed toward the preparation of methotrexate-loaded surface-modified solid lipid nanoparticles (SLNs) for potential use as a chemotherapeutic formulation for cancer therapy. A lipid (C14-AAP) derived from myristic acid (C14H30O2) and acetaminophen (AAP) was employed as a targeting ligand for human breast and lung cancer cells that overexpress the cyclooxygenases-2 (COX-2) enzyme. The SLNs consisting of stearic acid and C14-AAP were characterized by several methods, including dynamic light scattering (DLS), differential scanning calorimetry (DSC), powder X-ray diffraction (PXRD), ultraviolet-visible (UV-vis) spectroscopy, high-resolution transmission electron microscopy (HRTEM), and field emission scanning electron microscopy (FESEM) techniques. An in vitro cell cytotoxicity study was done by carrying out an MTT assay and flow cytometry study in the human breast cancer (MCF7) and human lung cancer cell line (A549). The expression level of COX-2 enzyme in MCF7 and A549 cell lines was examined by reverse transcription polymerase chain reaction (RT-PCR). A high level of COX-2 expression was observed in both cell lines. In vitro cell cytotoxicity study in MC7 and A549 cell lines showed the surface-modified, methotrexate-loaded SLN is more effective in cell killing and induction of apoptotic death in both the cell lines than free methotrexate in MTT, flow cytometry, clonogenic assay, and Western blot studies. The surface-modified SLN was radiolabeled with 99mTc with %RCP greater than 95%. In vivo biodistribution study of the 99mTc-labeled SLN in melanoma tumor-bearing C57BL6 mice showed moderate tumor uptake of the radiotracer at 3 h post injection. The SPECT/CT image aligns with the biodistribution results. This study shows that AAP-modified SLNs could be a potential chemotherapeutic formulation for cancer therapy.