Antibody conjugated lipid nanoparticles as a targeted drug delivery system for hydrophobic pharmaceuticals.

ABSTRACT

Cancer remains a significant health issue worldwide. The most common group of chemotherapeutic agents are small-molecule drugs, which often are associated with toxic side-effects and non-specific delivery, leading to limited therapeutic effect. This paper describes the development of a targeted drug delivery system based on lipid nanoparticles for cancer therapy. The lipid nanoparticles consist of a lipid core conjugated to an albumin stealth coating and targeting antibodies through thiol chemistry synthesized utilizing a one-step method. Applying the developed method, lipid nanoparticles with diameters down to 87 nm, capable of encapsulating small molecule compounds were synthesized. Cellular uptake studies of the lipid nanoparticles loaded with the model drug Nile red demonstrated that stealth-coating reduced non-specific cell uptake by up to a 1000-fold compared to free drug. Moreover, antibody-conjugation led to a significant cellular retargeting. Finally, it was shown that the lipid nanoparticles undergo cellular uptake through the endocytic pathway. The lipid nanoparticles are simple to synthesize, stabile in serum and have the potential to be versatile targeted towards receptors selectively expressed by diseased cells using antibodies. Thus, the system may reduce the toxic side-effects of cancer drugs while improving their delivery to cancer cells, increasing the therapeutic effect.