Half generations magnetic PAMAM dendrimers as an effective system for targeted gemcitabine delivery

Mutlu, Pelin
Yalcin, Serap
Tezcaner, Ayşen
Gündüz, Ufuk
Tumor-specific delivery of anticancer drugs by magnetic nanoparticles will maximize the efficacy of the drug and minimize side effects, and reduce systemic toxicity. The magnetic core of these nanoparticles provides an advantage for selective drug targeting as they can be targeted to the tumor site and accumulated in cancer cells by means of an external magnetic field. Magnetic nanoparticles can be coated with Polyamidoamine (PAMAM) dendrimer and loaded with drugs. However, biomedical applications of PAMAM dendrimers are limited due to their toxicity associated with their multiple cationic charges due to terminal -NH2 groups. Modifying the positively charged end groups with negatively charged -COOH groups, is a satisfactory strategy for obtaining less toxic PAMAM dendrimers. Gemcitabine being an analogue of deoxycytidine, is an effective anticancer drug. However, clinical benefits of Gemcitabine are limited due to its short biological half-life. The aim of this study was to obtain an effective, less toxic targeted delivery system for Gemcitabine. Half generations, between G4.5 and G7.5, of PAMAM dendrimer coated magnetic nanoparticles (DcMNPs) were synthesized and conjugated with Gemcitabine. TEM images showed nanoscale size (12-14 nm) of the nanoparticles. The zeta-potential analysis indicated a decreased negativity of surface charge in drug bound dendrimer compared to the empty nanoparticles. Gemcitabine was effectively conjugated successfully onto the surface of half-generations of PAMAM DcMNPs. It was observed Gemcitabine did not effectively bind to Generations G4 and G5. The highest drug loading was obtained for DcMNPs with Generation 5.5. Empty nanoparticles showed no significant cytotoxicity on SKBR-3 and MCF-7 cells. On the other hand, Gemcitabine loaded nanoparticles were 6.0 fold more toxic on SKBR-3 and 3.0 fold more toxic on MCF-7 cells compared to free Gemcitabine. Gemcitabine loaded on Generation 5.5 DcMNPs showed a higher stability than free Gemcitabine. About 94% of the drug was retained over 6 weeks period, at pH 7.2. Due to their targetability under magnetic field, stability, size distribution, cellular uptake and toxicity characteristics the dendrimeric nanoparticles obtained in this study can be useful a delivery system for Gemcitabine in cancer therapy.


Poly (I:C)- and doxorubicin-loaded magnetic dendrimeric nanoparticles affect the apoptosis-related gene expressions in MCF-7 cells
Khodadust, Rouhollah; Alpsoy, Aktan; Ünsoy, Gözde; Gündüz, Ufuk (The Scientific and Technological Research Council of Turkey, 2020-8-19)
Use of nanoparticles as drug carrier vectors has great potential to circumvent the limitations associated with chemotherapy, including drug resistance and destructive side effects. For this purpose, magnetic generation 4 dendrimeric nanoparticles were prepared to carry chemotherapeutic agent doxorubicin (G 4-DOX) and immune modulator polyinosinic:polycytidylic acid [Poly(I:C)]. As previously reported, DOX and Poly(I:C) was loaded onto G 4 nanoparticles (PIC-G 4-DOX). Cellular internalization study using con...
Loading of Gemcitabine on chitosan magnetic nanoparticles increases the anti-cancer efficacy of the drug
PARSIAN, Maryam; UNSOY, Gozde; Mutlu, Pelin; Yalcin, Serap; Tezcaner, Ayşen; Gündüz, Ufuk (2016-08-05)
Targeted delivery of anti-cancer drugs increase the efficacy, while decreasing adverse effects. Among various delivery systems, chitosan coated iron oxide nanoparticles (CsMNPs) gained attention with their biocompatibility, biodegradability, low toxicity and targetability under magnetic field. This study aimed to increase the cellular uptake and efficacy of Gemcitabine.
Nanoparticle-based drug delivery in cancer: the role of cell membrane structures
Yalcin, Serap; Ozluer, Ozlem; Gündüz, Ufuk (2016-11-01)
Development of novel drug-delivery systems aims to specifically deliver anticancer drugs to tumor tissues and improve the efficiency of chemotherapy, while minimizing side effects of drugs on healthy tissues and organs. However, drug-delivery systems are confronted by membrane barriers and multiple drug resistance in cancer cells. In recent years, the obtained results indicate an important role of lipids, proteins and carbohydrates in apoptosis, drug transport and the process of cellular uptake of nanoparti...
Expression analysis of TOP2A, MSH2 and MLH1 genes in MCF7 cells at different levels of etoposide resistance
Kaplan, Esra; Gündüz, Ufuk (2012-02-01)
Purpose: Development of resistance against anti-cancer drugs is one of the major obstacles of chemotherapy in the treatment of cancer. Etoposide is a topoisomerase II alpha (TOP2A) inhibitor, which is used in the treatment of breast cancer. Alterations in the expression of drug targets or DNA repair genes are among the important resistance mechanisms against TOP2A inhibitors. In this study, expression changes in TOP2A gene and two important mismatch repair (MMR) genes MSH2 and MLH1 were examined in order to...
Synthesis and characterization of fatty acid based hyperbranched polymers for anti-cancer drug delivery
Güç, Esra; Gündüz, Ufuk; Department of Biology (2008)
Conventional methods of chemotherapy requires novel therapy systems due to serious side effects and inefficiency of drug administration. In recent years many studies are carried out to improve drug delivery systems. Polymers are one of the most important elements for drug delivery research due to their versatility. By the discovery of dendritic polymers, drug delivery studies gained a new vision. Highly branched monodisperse structure, multiple sites of attachment, well-defined size and controllable physica...
Citation Formats
M. PARSIAN, P. Mutlu, S. Yalcin, A. Tezcaner, and U. Gündüz, “Half generations magnetic PAMAM dendrimers as an effective system for targeted gemcitabine delivery,” INTERNATIONAL JOURNAL OF PHARMACEUTICS, pp. 104–113, 2016, Accessed: 00, 2020. [Online]. Available: https://hdl.handle.net/11511/31113.