Peptide nanosponges designed for rapid uptake by leukocytes and neural stem cells |
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| Authors: | Asanka S Yapa Hongwang Wang Sebastian O Wendel Tej B Shrestha Nilusha
L Kariyawasam Madumali Kalubowilage Ayomi S Perera Marla Pyle Matthew T Basel Aruni P Malalasekera Harshi Manawadu Jing Yu Yubisela Toledo Raquel Ortega Prem S Thapa Paul E Smith Deryl L Troyer Stefan H Bossmann |
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| Institution: | Department of Chemistry, Kansas State University, Manhattan KS 66506 USA, Fax: +1-785-532-6666, +1-785-532-6817 ; Department of Anatomy & Physiology, Kansas State University, Manhattan KS USA, +1-785-532-6405 ; Microscopy and Analytical Imaging Laboratory, University of Kansas, Lawrence KS USA |
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| Abstract: | The structure of novel binary nanosponges consisting of (cholesterol-(K/D)nDEVDGC)3-trimaleimide units possessing a trigonal maleimide linker, to which either lysine (K)20 or aspartic acid (D)20 are tethered, has been elucidated by means of TEM. A high degree of agreement between these findings and structure predictions through explicit solvent and then coarse-grained molecular dynamics (MD) simulations has been found. Based on the nanosponges'' structure and dynamics, caspase-6 mediated release of the model drug 5(6)-carboxyfluorescein has been demonstrated. Furthermore, the binary (DK20) nanosponges have been found to be virtually non-toxic in cultures of neural progenitor cells. It is of a special importance for the future development of cell-based therapies that DK20 nanosponges were taken up efficiently by leucocytes (WBC) in peripheral blood within 3 h of exposure. The percentage of live cells among the WBC was not significantly decreased by the DK20 nanosponges. In contrast to stem cell or leucocyte cell cultures, which have to be matched to the patient, autologous cells are optimal for cell-mediated therapy. Therefore, the nanosponges hold great promise for effective cell-based tumor targeting.Nanosponges for drug delivery. |
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