Targeted Drug Delivery via Chitosan-Coated Magnetic Nanoparticles

The devastating effects of chemotherapeutic agents have been observed on healthy cells as well as tumor cells because they are nonspecifically distributed all over the body. This treatment results in hazardous side effects and excessive toxicity. Targeted drug delivery has emerged to overcome the lack of specificity of conventional chemotherapy. Nanoparticles used for drug targeting are promising to circumvent these challenges, by enabling the localization of high drug amounts at the site of disease. When drugs are conjugated on nanoparticles, it is possible to increase their half-life while decreasing the side effects and improving therapeutic efficacy. Several therapeutic nanoparticles that selectively bind and target cancer cells have been approved for clinical use (Davis, M.E., Zuckerman, J.E., Choi, C.H.J., Seligson, D., Tolcher, A., Alabi, C.A., et al., 2010. Evidence ofRNAi in humans from systemically administered siRNA via targeted nanoparticles. Nature 464 (7291), 1067–1070.; Hrkach, J., Von Hoff, D., Ali, M.M., Andrianova, E., Auer, J., Campbell, T., et al., 2012. Preclinical developmentand clinical translation of a PSMA-targeted docetaxel nanoparticle with a differentiated pharmacologicalprofile. Sci. Transl. Med. 4 (128), 128ra39-128ra39; Tabernero, J., Shapiro, G.I., LoRusso, P.M., Cervantes, A., Schwartz, G.K., Weiss, G.J., et al., 2013. Firstin-humans trial of an RNA interference therapeutic targeting VEGF and KSP in cancer patients with liverinvolvement. Cancer Discov. 3 (4), 406–417). Surface modifications of nanoparticles with organic polymers enable the stabilization of nanoparticles, reduce agglomeration, provide functional groups for further alterations, furnish internal cavities for loading of therapeutics, and prevent immediate uptake of drug-loaded nanoparticles by the reticuloendothelial system. Polymer-coated magnetic nanoparticles, characterized by high surface to volume ratios, are excellent scaffolds for loading targeting moieties, permeation enhancers, imaging tags, and drugs, simultaneously providing diagnostic and therapeutic capabilities. Multifunctionality of nanoparticle constructs can facilitate combination therapies. Nanoparticles can be routed to the tumor tissue via passive or active targeting. Nanotechnology has the potential to change cancer diagnosis and therapy fundamentally, which may bring new insights to the chemotherapy

Development of poly (I:C) modified doxorubicin loaded magnetic dendrimer nanoparticles for targeted combination therapy

The objective of this study was to develop and evaluate the anticancer activity and the safety of a combinational drug delivery system using polyamidoamine (PAMAM) dendrimer-coated iron oxide nanoparticles for doxorubicin and poly I:C delivery in vitro. Dendrimer-coated magnetic nanoparticles (DcMNPs) are suitable for drug delivery system as nanocarriers with their following properties, such as surface functional groups, symmetry perfection, internal cavities, nano-size and magnetization. These nanoparticles could be targeted to the tumor site under a magnetic field since they have a magnetic core. DcMNPs were found as a convenient vehicle for targeted doxorubicin delivery in cancer therapy. Poly (I:C) binding on doxorubicin loaded DcMNPs (DcMNPs-Dox) was reported for the first time in the literature. It was also demonstrated that loading of doxorubicin into the cavities of DcMNPs increases the binding efficiency of poly (I:C) to the surface functional groups of dendrimer up to 10 times. When we compare the in vitro cytotoxic properties of doxorubicin, poly (I:C) and poly (I:C) bound doxorubicin loaded DcMNPs (PIC-DcMNPs-Dox), it was observed that PIC-DcMNPs-Dox show the highest cytotoxic effect by passing the cell resistance mechanisms on doxorubicin resistant MCF7 (MCF7/Dox) cells. Results demonstrated that applying PIC-DcMNPs-Dox would improve the efficacy by increasing the biocompatibility of system in blood stream and the toxicity inside tumor cells. These results provide invaluable information and new insight for the design and optimization of a novel combinational drug delivery system for targeted cancer therapy. (C) 2014 Elsevier Masson SAS. All rights reserved

Doksorubisin Bağlı Kitosan Kaplı Manyetik Nanoparçacıkların Meme Kanseri Hücre Hatları Üzerindeki Etkinliğinin İmmünositokimya Yöntemi İle Belirlenmesi

Nanoparçacıkların kanser tedavisi, ilaç hedefleme ve kontrollü ilaç salım sistemlerinde kullanımı çalışmaları son zamanlarda artış göstermektedir. Nanoparçacıklar küçük boyutları sayesinde hücre içine kolay alınabilmekte ve çeşitli malzemelerle kaplanarak yüzey özellikleri değiştirilebilmektedir. Tümör hücrelerine hedeflendirilebilen manyetik nanoparçacıklar (MNP) kanser tanı ve tedavisinde kullanılmaktadır. Manyetik özellik taşıyan nanoparçacıklar, manyetik alan varlığında istenilen bölgeye hedeflenebilme özellikleri sayesinde ilaç hedefleme ve kontrollü salıma yeni bir boyut kazandırmıştır. Dışarıdan uygulanan manyetik alan tarafından kolayca kontrol edilebilen bu tür nanoparçacıklar, yeterli miktarda anti-kanser ilacın hücrelere taşınmasında etkili olmaktadır. Bu çalışmada manyetik özellikli kitosan kaplı nanoparçacıkların sentezlenmesi, anti kanser bir ilaç olan Doksorubisin’in nanoparçacıklara yüklenmesi ve in vitro koşullarda nanoparçacıkların MCF-7 meme kanseri hücre hatlarına uygulanması amaçlanmaktadır. Sentezlenen kitosan kaplı nanoparçacıkların merkezinde bulunan manyetit (Fe3O4) demiroksit nanoparçacıklara manyetik özellik sağlayacaktır. Kitosan polimeri ile kaplı olarak sentezlenen MNP’lerin karakterizasyonu yapıldıktan sonra, MNP’lere doksorubisin ilacı yüklenecektir. Oluşturulan yapının karakteristik özellikleri belirlenecek ve in vitro koşullarda istenilen hücrelere yönlendirilebilme özellikleri incelenecektir. MCF-7 meme kanseri hücre hatları üzerindeki toksik etkileri sitotoksisite analizleri ile araştırılacaktır. Projenin son kısmında, Doksorubisin yüklü nanoparçacıkların MCF-7 hücre hatları üzerindeki etkinliği immünositokimya yöntemi ile belirlenecektir

Preparation of fluorescent IgG monoclonal antibody conjugated PHB coated magnetic nonoparticles for imaging and cancer therapy

FEBS EMBO 2014 Conference -- AUG 30-SEP 04, 2014 -- Paris, FRANCEWOS: 000359666803183…FEBS, EMB

PAMAM dendrimer-coated iron oxide nanoparticles: synthesis and characterization of different generations

This study focuses on the synthesis and characterization of different generations (G(0)-G(7)) of polyamidoamine (PAMAM) dendrimer-coated magnetic nanoparticles (DcMNPs). In this study, superparamagnetic iron oxide nanoparticles were synthesized by co-precipitation method. The synthesized nanoparticles were modified with aminopropyltrimethoxysilane for dendrimer coating. Aminosilane-modified MNPs were coated with PAMAM dendrimer. The characterization of synthesized nanoparticles was performed by X-ray diffraction, X-ray photoelectron spectroscopy (XPS), Fourier transform infrared spectroscopy (FTIR), transmission electron microscopy (TEM), dynamic light scattering, and vibrating sample magnetometry (VSM) analyses. TEM images demonstrated that the DcMNPs have monodisperse size distribution with an average particle diameter of 16 +/- 5 nm. DcMNPs were found to be superparamagnetic through VSM analysis. The synthesis, aminosilane modification, and dendrimer coating of iron oxide nanoparticles were validated by FTIR and XPS analyses. Cellular internalization of nanoparticles was studied by inverted light scattering microscopy, and cytotoxicity was determined by XTT analysis. Results demonstrated that the synthesized DcMNPs, with their functional groups, symmetry perfection, size distribution, improved magnetic properties, and nontoxic characteristics could be suitable nanocarriers for targeted cancer therapy upon loading with various anticancer agents

Doxorubicin loading, release, and stability of polyamidoamine dendrimer-coated magnetic nanoparticles

WOS: 000319071200016PubMed ID: 23558592Nanotechnology is a promising alternative to overcome the limitations of classical chemotherapy. As a novel approach, dendrimer-coated magnetic nanoparticles (DcMNPs) maintain suitable drug delivery system because of their buildup of functional groups, symmetry perfection, nanosize, and internal cavities. They can also be targeted to the tumor site in a magnetic field. The aim of this study is to obtain an effective targeted delivery system for doxorubicin, using polyamidoamine (PAMAM) DcMNPs. Different generations (G2, G3, G4, and G7) of PAMAM DcMNPs were synthesized. Doxorubicin loading, release, and stability efficiencies in these nanoparticles (NPs) were studied. The results showed that low-generation NPs obtained in this study have pH-sensitive drug release characteristics. G4DcMNP, which releases most of the drug in lower pH, seems to be the most suitable generation for efficient Doxorubicin delivery. Furthermore, application of doxorubicin-loaded G4DcMNPs may help to overcome doxorubicin resistance in MCF-7 cells. On the contrary, G2 and G3DcMNPs would be suitable for the delivery of drugs such as vinca alkaloids (Johnson IS, Armstrong JG, Gorman M, Burnett JP. 1963. Cancer Res 23:13901427.) and taxenes (Clarke SJ, Rivory LP. 1999. Clin Pharmacokinet 36(2):99114.), which show their effects in cytoplasm. The results of this study can provide new insights in the development of pH-sensitive targeted drug delivery systems to overcome drug resistance during cancer therapy. (c) 2013 Wiley Periodicals, Inc. and the American Pharmacists Association J Pharm Sci 102:18251835, 2013TUBITAKTurkiye Bilimsel ve Teknolojik Arastirma Kurumu (TUBITAK) [TBAG-109T949, TBAG-2215]; Middle East Technical UniversityMiddle East Technical University [BAP-07-02-2010-06]This study was supported by TUBITAK (TBAG-109T949 and TBAG-2215) and Middle East Technical University (BAP-07-02-2010-06)