Rameshwer Shukla et al 2008 Nanotechnology 19 295102 doi:10.1088/0957-4484/19/29/295102
HER2 specific delivery of methotrexate by dendrimer conjugated anti-HER2 mAb
Rameshwer Shukla, Thommey P Thomas, Ankur M Desai, Alina Kotlyar, Steve J Park and James R Baker Jr
Show affiliationsHerceptin, a humanized monoclonal antibody that binds to human growth factor receptor-2 (HER2), was covalently attached to a fifth-generation (G5) polyamidoamine dendrimer containing the cytotoxic drug methotrexate. The specific binding and internalization of this conjugate labeled with FITC was clearly demonstrated in cell lines overexpressing HER2 by flow cytometry as well as confocal microscopic analysis. In addition, binding and uptake of antibody conjugated dendrimers was completely blocked by excess non-conjugated herceptin. The dendrimer conjugate was also shown to inhibit the dihydrofolate reductase with similar activity to methotrexate. Co-localization experiments with lysotracker red indicate that antibody conjugate, although internalized efficiently into cells, has an unusually long residence time in the lysosome. Somewhat lower cytotoxicity of the conjugate in comparison to free methotrexate was attributed to the slow release of methotrexate from the conjugate and its long retention in the lysosomal pocket.
- PACS
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47.63.mh Transport processes and drug delivery
87.15.N- Properties of solutions of macromolecules
- Subjects
- Dates
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Issue 29 (23 July 2008)
Received 3 April 2008, in final form 9 May 2008
Published 10 June 2008
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HER2 specific delivery of methotrexate by dendrimer conjugated anti-HER2 mAb
Rameshwer Shukla et al 2008 Nanotechnology 19 295102
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Transformational optics of plasmonic metamaterials
I I Smolyaninov 2008 New J. Phys. 10 115033
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Peer review statement
2008 J. Phys.: Conf. Ser. 192 011002
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Nanoscale in situ investigation of ultrathin silicon oxide thermal decomposition by high temperature scanning tunneling microscopy
K Xue et al 2007 Nanotechnology 18 485709
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An indirect search for dark matter using antideuterons: the GAPS experiment
C J Hailey 2009 New J. Phys. 11 105022
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Classification of coupled systems with two-component nonlinear diffusion equations by the invariant subspace method
Changzheng Qu and Chunrong Zhu 2009 J. Phys. A: Math. Theor. 42 475201
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Probing medium-range structural correlations by fluctuation microscopy
M M J Treacy et al 2007 J. Phys.: Condens. Matter 19 455201
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An effective Dirac equation for a binary of two fermions
E Marsch 2008 J. Phys. A: Math. Theor. 41 185301
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Searches for gravitational waves associated with pulsar glitches using a coherent network algorithm
K Hayama et al 2008 Class. Quantum Grav. 25 184016
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Molecular dynamics simulation of nanoindentaiton on ion-induced damage of silicon surface
S Satake et al 2009 J. Phys.: Conf. Ser. 191 012011
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