富列那酮（Fulvestrant, F）、拉帕替尼（Lapatinib, L）和紫杉醇（Paclitaxel, P）是疏水性抗癌药物，用于治疗雌激素受体（ER）和表皮生长因子受体（EGFR）阳性的乳腺癌。本研究合成了以靶向肿瘤细胞为目标的F、L和/或P取代的糠醛化PAMAM G4树状分子，并对其进行了表征，比较性测试了其对胶质瘤U-118 MG和非小细胞肺癌A549细胞的抗肿瘤活性，并与人类非肿瘤原生角质形成细胞（HaCaT）进行比较。所有细胞系均为ER+和EGFR+。此外，还对所述药物在秀丽隐杆线虫（C. elegans）的抗秀丽病的治疗环境中进行了测试。结果显示，具有水溶性的G4P、G4F、G4L和G4PFL共轭物通过内吞作用主动进入测试细胞，这是由于其正电ζ电位（在13.57-40.29 mV之间）和纳米粒子直径为99-138 nm。纳摩尔浓度的G4P和G4PFL共轭物显示出最高的活性，而最不活性的共轭物则是G4F。这些共轭物抑制了HaCaT和A549细胞的增殖；在胶质瘤细胞中，细胞毒性主要与细胞损伤（线粒体和膜转运）有关。共轭物的毒性与所附药物残留的数量成正比，但G4L是个例外；其对胶质瘤和角质形成细胞的作用分别比单独使用拉帕替尼增强两倍和八倍。不幸的是，非癌症HaCaT细胞对所测试构建物最敏感，这迫使改变了以ER和EGFR受体作为癌症治疗目标的方法。对C. elegans的体内研究表明，所有化合物，尤其是G4PFL，可能潜在地在驱虫治疗中有用。

Fulvestrant (F), lapatinib (L), and paclitaxel (P) are hydrophobic, anticancer drugs used in the treatment of estrogen receptor (ER) and epidermal growth factor receptor (EGFR)-positive breast cancer. In this study, glycidylated PAMAM G4 dendrimers, substituted with F, L, and/or P and targeting tumor cells, were synthesized and characterized, and their antitumor activity against glioma U-118 MG and non-small cell lung cancer A549 cells was tested comparatively with human non-tumorogenic keratinocytes (HaCaT). All cell lines were ER+ and EGFR+. In addition, the described drugs were tested in the context of antinematode therapy on C. elegans. The results show that the water-soluble conjugates of G4P, G4F, G4L, and G4PFL actively entered the tested cells via endocytosis due to the positive zeta potential (between 13.57-40.29 mV) and the nanoparticle diameter of 99-138 nm. The conjugates of G4P and G4PFL at nanomolar concentrations were the most active, and the least active conjugate was G4F. The tested conjugates inhibited the proliferation of HaCaT and A549 cells; in glioma cells, cytotoxicity was associated mainly with cell damage (mitochondria and membrane transport). The toxicity of the conjugates was proportional to the number of drug residues attached, with the exception of G4L; its action was two- and eight-fold stronger against glioma and keratinocytes, respectively, than the equivalent of lapatinib alone. Unfortunately, non-cancer HaCaT cells were the most sensitive to the tested constructs, which forced a change in the approach to the use of ER and EGFR receptors as a goal in cancer therapy. In vivo studies on C. elegans have shown that all compounds, most notably G4PFL, may be potentially useful in anthelmintic therapy.