"Smart" lipid microbubbles for targeting and drug delivery

“Smart” lipid microbubbles for targeting and drug delivery Gaio Paradossi, Barbara Cerroni, Letizia Oddo Dipartimento di Scienze e Tecnologie Chimiche, Università di Roma Tor Vergata, Via della Ricerca Scientifica 1, 00133 Rome, Italy. Lipid microbubbles are known as ultrasound contrast agents (UCAs). They consist of hydrophobic gas, tipically a perfluorocarbon or sulfur hexafluoride, encapsulated by a shell of surfactant molecules assembled as monolayer. To address UCAs on tumor endothelial cells, we decorated their surface with the cyclic pentapeptide, cyclo(Arg-Gly-Asp-D-Phe-Cys) ), containing the sequence RGD, or its analog cyclo(Arg-Ala-Asp-D-Phe-Cys) with a RAD sequence as positive control. RGD sequence is recognized by integrins, the transmembrane proteins overexpressed by tumor endothelial cells or human umbilical vein endothelial cells (HUVEC). In this contribution we tested the bioadhesion of RGD decorated UCAs under controlled and realistic flow conditions such as shear rate, channel diameter, temperature on HUVEC and, as positive control, on fibrablasts NIH3T3 cell lines. Sonoporation, the reversible opening of cell membrane upon ultrasound irradiation, can be a method to favor the internalization of drugs. However, a careful optimization of the process is needed to warrant cells viability. The presence of the microbubbles affects the efficiency of the method. This research has been supported by the FP7 Eu project “TheraGlio”. “Smart” lipid microbubbles for targeting and drug delivery Gaio Paradossi, Barbara Cerroni, Letizia Oddo Dipartimento di Scienze e Tecnologie Chimiche, Università di Roma Tor Vergata, Via della Ricerca Scientifica 1, 00133 Rome, Italy. Lipid microbubbles are known as ultrasound contrast agents (UCAs). They consist of hydrophobic gas, tipically a perfluorocarbon or sulfur hexafluoride, encapsulated by a shell of surfactant molecules assembled as monolayer. To address UCAs on tumor endothelial cells, we decorated their surface with the cyclic pentapeptide, cyclo(Arg-Gly-Asp-D-Phe-Cys) ), containing the sequence RGD, or its analog cyclo(Arg-Ala-Asp-D-Phe-Cys) with a RAD sequence as positive control. RGD sequence is recognized by integrins, the transmembrane proteins overexpressed by tumor endothelial cells or human umbilical vein endothelial cells (HUVEC). In this contribution we tested the bioadhesion of RGD decorated UCAs under controlled and realistic flow conditions such as shear rate, channel diameter, temperature on HUVEC and, as positive control, on fibrablasts NIH3T3 cell lines. Sonoporation, the reversible opening of cell membrane upon ultrasound irradiation, can be a method to favor the internalization of drugs. However, a careful optimization of the process is needed to warrant cells viability. The presence of the microbubbles affects the efficiency of the method. This research has been supported by the FP7 Eu project “TheraGlio”.