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Molecular Engineering in Nanotechnology. II. Structure and Composition of Multifunctional Devices for Medical Application

Balazs L. Keszler, Istvan J. Majoros*, and James R. Baker Jr.

Center for Biologic Nanotechnology, University of Michigan,
Ann Arbor, MI 48109 USA

This is an abstract for a presentation given at the
Ninth Foresight Conference on Molecular Nanotechnology.
There will be a link from here to the full article when it is available on the web.

 

Dendrimers with discrete numbers and high local densities of surface functionalities in one molecule are very attractive for biomedical applications, especially in cancer therapy. The dendritic multifunctional platform is ideal to combine various functions like imaging, targeting and drug transfer into cell. In Part 1. we have demonstrated the successful synthesis of such multifunctional nanodevice based on generation-5 (G5) PAMAM dendrimer (fluorescein (FITC) for imaging, folic acid for targeting, taxol and methotrexate for drug functionalities).

In this work, we present evidences that support and verify the structure and functionalities of the multifunctional device. Theoretically, there are 128 primary amine groups on the surface of the G5 dendrimer. Potentiometric titration accounted for 120 amine groups indicating sight defect in the structure. 80%, that is 96 primary amino groups were acetylated to improve solubility in aqueous media, which left 24 amino groups for further functionalization. Molecular weights (Mn, Mw) and molecular weight distributions (MWD) were determined by Alliance Waters 2690 GPC equipped with Waters 2487 UV, Wyatt DAWN DSP MALLS and Optilab DSP Interferometric Refrac-tometer before and after acetylation. Data are summarized in Table 1. The measured molecular weight data correlate with the titration data and indicate mono-modal structure with small deviation from perfection.

Table 1.
Parameters G5 Acylated G5
theoretical measured theoretical measured
Mn 28826 26040 32858 30290
Mw 28826 26640 32858 31530
MWD 1.000 1.023 1.000 1.041

Fluorescein, folic acid (at 280 nm), taxol (at 227 nm) and methotrexate (at 280 nm) functionalities were characterised by UV spectroscopy using Perkin Elmer UV/VIS Spectrometer Lambda 20. Data are listed in Table 2.

Table 2.
Units on G5 surface
FITC Folic Acid Taxol Metotrexate
amid bond ester bond
5 3 2 5 2

Based on the experimental results the synthesized multifunctional nanodevices have the following structure and compositions: G5-(acetamide)96-(FITC)5-(Folic Acide)3-(Taxol)2, G5-( acetamide)96-(FITC)5-(Folic Acide)3-(Methotrexate(ester))2, G5-(acetamide)96-(FITC)5-(Folic Acide)3-(Methotrexate(amid))5, respectively. The delivery and targeting efficiency and cytotoxicity of the devices were tested in vitro on KB cell line.

Abstract in RTF format 12,945 bytes


*Corresponding Address:
Istvan Majoros
Center for Biologic Nanotechnology, University of Michigan
200 Zina Pitcher, 4026 Kresge II, Ann Arbor, MI 48109 USA
phone: 734-615-0618
fax: 734-615-0621
email: majoros@umich.edu



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