Dendrimer-based targeted drug delivery, as an innovative polymeric drug-delivery system, is promising for cancer therapy. Folate receptors (FR) are overexpressed in many types of tumor cells, such as breast cell carcinomas, which allow folate-targeted delivery. Therefor polyethylene glycol (PEG) modified-PAMAM G4 dendrimers were functionalized with folic acid (FA), as targeting agent. Then, 5-FU (5-fluorouracil) and ^99mTc (technetium-99 m) as therapeutic agents were respectively loaded and conjugated to previous nano-complex (PEG-PAMAM G4-FA-5FU-^99mTc). The value of drug loading was calculated by TGA analysis (16.97%). Drug release profiles of PEG-PAMAM G4-FA-5FU-^99mTc and PEG-PAMAM G4-FA-5FU were evaluated. The radiochemical purity of PEG-PAMAM G4-FA-5FU-^99mTc and PEG-PAMAM G4-FA-^99mTc was obtained at >95% with excellent in-vitro and in-vivo stabilities. PEG-PAMAM G4-FA-5FU-^99mTc was synthesized and the stability studies were carried out by the ITLC methods in serum (86.67% and 83.75%) and PBS. Combinational therapy effects of 5-FU and ^99mTc containing nano-complexes were evaluated on 4 T1 (mouse breast cancer) and MDA-MB-231 (human breast adenocarcinoma) cancer cell lines. Excellent uptake values were obtained for FA-decorated nano-complexes on 4 T1 and MDA-MB-231 cell lines. Subsequently, tumor inhibition effects of PEG-PAMAM G4-FA-5FU-^99mTc and PEG-PAMAM G4-FA-5FU were evaluated using the breast tumor-bearing BALB/C mice.

Breast Tumor Targeting with PAMAM-PEG-5FU- ^99mTc As a New Therapeutic Nanocomplex: in In-vitro and In-vivo Studies was presented. This targeted drug delivery system can significantly increase the efficiency of cancer therapy, and reduce the treatment cost and time.

中文翻译：

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以PAMAM-PEG-5FU-99mTc靶向乳腺癌作为一种新型治疗纳米复合物：体内和体外研究。

基于树状大分子的靶向药物递送作为一种创新的聚合物药物递送系统，有望用于癌症治疗。叶酸受体（FR）在许多类型的肿瘤细胞（例如乳腺癌细胞）中过表达，这些肿瘤细胞允许叶酸靶向递送。因此，用叶酸（FA）作为靶向剂将聚乙二醇（PEG）修饰的-PAMAM G4树状聚合物官能化。然后，分别加载5-FU（5-氟​​尿嘧啶）和^99m Tc（tech 99 m）作为治疗剂，并与先前的纳米复合物（PEG-PAMAM G4-FA-5FU- ^99m Tc）偶联。通过TGA分析计算载药量的值（16.97％）。评价了PEG-PAMAM G4-FA-5FU - ^99m Tc和PEG-PAMAM G4-FA-5FU的药物释放曲线。PEG-PAMAM G4-FA-5FU-的放射化学纯度^获得99m Tc和PEG-PAMAM G4-FA- ^99m Tc，其> 95％具有出色的体外和体内稳定性。合成了PEG-PAMAM G4-FA-5FU- ^99m Tc，并通过ITLC方法在血清（86.67％和83.75％）和PBS中进行了稳定性研究。评价了5-FU和^99m Tc纳米复合物的联合治疗效果对4种T1（小鼠乳腺癌）和MDA-MB-231（人乳腺癌）癌细胞系的作用。FA装饰的纳米复合物在4种T1和MDA-MB-231细胞系上均获得了极好的摄取值。随后，PEG-PAMAM G4-FA-5FU- ^99m的肿瘤抑制作用使用荷乳腺肿瘤的BALB / C小鼠评估了Tc和PEG-PAMAM G4-FA-5FU。

以PAMAM-PEG-5FU- ^99m Tc作为新的治疗纳米复合物的乳腺癌靶向治疗：在体外和体内研究中均已提出。这种靶向药物递送系统可以显着提高癌症治疗的效率，并减少治疗成本和时间。