Targeted poly (l-纬-glutamyl glutamine) nanoparticles of docetaxel against folate over-expressed breast cancer cells

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• 作者：Faranak Tavassolian^a ; ^b ; Golnaz Kamalinia^a ; ^b ; Hasti Rouhani^a ; ^b ; Mohsen Amini^c ; ^d ; Seyed Nasser Ostad^e ; Mohammad Reza Khoshayand^f ; Fatemeh Atyabi^a ; ^b ; Morteza Rafiee Tehrani^a ; Rassoul Dinarvand^a ; ^b ; ^{dinarvand@tums.ac.ir" class="auth_mail}
• 关键词：Nanoparticles ; Folate targeting ; Poly(l-纬-glutamyl glutamine) ; MTT assay ; Docetaxel ; Antitumor efficacy
• 刊名：International Journal of Pharmaceutics
• 出版年：5 June 2014
• 年：2014
• 卷：467
• 期：1-2
• 页码：123-138
• 全文大小：3501 K

文摘

A novel folate (FA) conjugated poly(l-纬-glutamyl glutamine) (PGG) nanoparticle loaded with docetaxel (DTX) was prepared to take advantage of both targeted drug delivery in breast cancer and reducing the overall side effects due to the adjuvant free formulation in comparison with Taxotere^®. Nanoprecipitation method was employed to prepare nanoparticles (NPs). The chemical structure of PGG synthesized polymers and PGG-FA conjugates and polymeric nanoparticles were characterized by H NMR, FTIR spectroscopy, field emission scanning electron microscopy, and laser scanning confocal microscopy. The average size of optimized nanoparticles with the aid of Box–Behnken experimental design was 131.96 ± 5.34 (nm) with polydispersity of 0.089 ± 0.019, zeta potential of −25.8 ± 2.21 (mV), and entrapment efficiency of 67.83 ± 3.29(%). In vitro cytotoxicity of the designed NPs was investigated by MTT assay against three chosen cell lines of MCF7, 4T1, and A549 based on their folate receptor expression capacity and was compared with Taxotere^®. Moreover, PGG-FOL NPs were loaded with 6-coumarin for cellular uptake investigation. In order to assess the antitumor efficacy and biodistribution of targeted NPs, 4T1 murine breast tumors were established on the balb/c mice and in vivo studies were performed. The obtained results showed that the novel designed system was highly effective against tumor cells and successfully localized in the tumor site.