Breast Tumor Targeting with PAMAM-PEG-5FU-99mTc As a New Therapeutic Nanocomplex: In In-vitro and In-vivo studies

Asghar Narmani | Monire Alsadat Afzali Arani | Javad Mohammadnejad | Ali Zaman Vaziri | Sedigheh Solymani | Kamal Yavari | Simin Janitabar Darzi | Farideh talebi

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URL :   http://research.shahed.ac.ir/WSR/WebPages/Report/PaperView.aspx?PaperID=159271
Date :  2020/04/25
Publish in :    Biomedical Microdevices
DOI :  https://doi.org/10.1007/s10544-020-00485-5
Link :  http://dx.doi.org/10.1007/s10544-020-00485-5
Keywords : 5-FU delivery; 99mTc; Breast cancer; Folic acid targeting; PAMAM G4-PEG

Abstract :

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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 Tc (technetium-99 m) as therapeutic agents were respectively loaded and conjugated to previous nano-complex (PEG-PAMAM G4-FA-5FU- Tc). The value of drug loading was calculated by TGA analysis (16.97). Drug release profiles of PEG-PAMAM G4-FA-5FUTc and PEG-PAMAM G4-FA-5FU were evaluated. The radiochemical purity of PEG-PAMAM G4-FA5FU- Tc and PEG-PAMAM G4-FA- Tc was obtained at 95 with excellent in-vitro and in-vivo stabilities. PEG-PAMAM G4-FA-5FU- Tc 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 Tc containing nano-complexes were evaluated on 4 T1 (mouse breast cancer) and MDA-MB231 (human breast adenocarcinoma) cancer cell lines. Excellent uptake values were obtained for FAdecorated nano-complexes on 4 T1 and MDA-MB-231 cell lines. Subsequently, tumor inhibition effects of PEG-PAMAM G4-FA-5FU- Tc and PEG-PAMAM G4-FA-5FU were evaluated using the breast tumor-bearing BALB/C mice. Graphical abstract Breast Tumor Targeting with PAMAM-PEG5FU- Tc 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.