LDL-conjugated to GM۱ micelles incorporating anticancer drugs to improve tumor cell uptake

Objective(s): The role of lipoproteins (LDL) as active molecules with preferential tumor interaction, but limited drug delivery capacity, has been previously reported. On the other hand, in a previous report, we demonstrated the high capacity of monosialogangliosides (GM۱) micelles as drug transporters. Materials and Methods: In this work, GM۱ was loaded with high doses of oncologic drugs such Paclitaxel or Doxorubicin and binded to LDL lipoproteins to form GM۱-drug-LDLwater soluble complex. Evidence suggests that both, hydrophobic and electrostatic forces, participate in the interaction, regulated by conditions such as pH, temperature and ionic strength.Results: Results of DLS and TEM show that GM۱-LDL complexes are considerably larger than the sum of their individual compounds, with a high charge of electronegative surface (-۵۵.۹ mV). In addition, the cytotoxic effect on cell cultures is greater when drugs are contained in GM۱-LDL complexes than when loaded in GM۱ micelles. Conclusion: The results suggest the participation of active energy-dependent mechanism in the uptake of GM۱-LDL drug, probably linked to the LDL receptor by the tumor cells. However, we could not confirm that the transport through LDL receptors is the only one that participates in the cellular uptake of the micelles.

Keywords:

GM۱-LDL , Micelles , Nanodelivery , Oncological drugs , Lipoproteins