Granulocyte Colony-Stimulating Factor Nanocarriers for Stimulation of the Immune System (Part I): Synthesis and Biodistribution Studies.

ABSTRACT

In the field of cancer immunotherapy, an original approach consists of using granulocyte colony-stimulating factor (G-CSF) to target and activate neutrophils, cells of the innate immune system. G-CSF is a leukocyte stimulating molecule which is commonly used in cancer patients to prevent or reduce neutropenia. We focused herein on developing a G-CSF nanocarrier which could increase the in vivo circulation time of this cytokine, keeping it active for targeting the spleen, an important reservoir of neutrophils. G-CSF-functionalized silica and gold nanoparticles were developed. Silica nanoparticles of 50 nm diameter were functionalized by a solid phase synthesis approach. The technology enabled us to incorporate multiple functionalities on the surface such as a PEG as hydrophilic polymer, DTPA as 111In chelating agent and G-CSF. The gold nanocarrier consisted of nanoparticles of 2-3 nm diameter elaborated with DTPA groups on the surface and functionalized with G-CSF. We studied the particle biodistribution in mice with special attention to organs involved in the immune system. The two nanocarriers with similar functionalization of surface showed different pathways in mice, probably due to their difference in size. Considering the biodistribution after G-CSF functionalization, we confirmed that the protein was capable of modifying the pharmacokinetics by increasing the nanocarrier concentration in the spleen, a reservoir of G-CSF receptor expressing cells.