Quantifying nanomedicine hitchhiking with neutrophils in solid tumors
Novel mechanistic studies in the field of drug delivery have elucidated an intricate compilation of tumor targeting mechanisms for passive and active targeting nanomedicines. On top of the identified traditional mechanisms, (i.e., passive diffusion and receptor targeting mechanisms), hitchhiking with myeloid cells (i.e., uptake of nanomedicines by circulating neutrophils and subsequent extravasation of the latter in the tumor microenvironment) has been discovered, by the applicants of this proposal, as a major contributor for the delivery of nanomedicines to malignant / inflamed regions. Past work had been conducted within the context of a previously approved proposal (FOTS-ID: 13178). In this current project, we aim to specifically quantify the contribution of “hitchhiking” as a mechanism for delivering nanomedicine formulations to the tumor microenvironment in triple negative breast cancer. By following this strategy, we will obtain a quantitative understanding of how endogenous immune cells are delivering nanomaterial in malignant lesions, and therefore pave the way for immunologicall-driven clinical solutions.
In this context, triple negative breast cancer (TNBC) orthotopic tumors will be grown in immunocompetent mice, and upon injection of nanoparticles (control and neutrophil-targeted) as well as selective neutrophil depletion, we will evaluate the nanoparticle targeting extent to solid tumors. Throughout the studies we will closely monitor the well-being of the mice. Upon appearance of significant discomfort, animals will be sacrificed. In total 160 mice will be used. Considering extensive in vitro and in vivo experimentation in the past, we aim to use the least animals possible. Moreover, if scientific merit is not compromised, we will reduce animal group sizes throughout the project.
In this context, triple negative breast cancer (TNBC) orthotopic tumors will be grown in immunocompetent mice, and upon injection of nanoparticles (control and neutrophil-targeted) as well as selective neutrophil depletion, we will evaluate the nanoparticle targeting extent to solid tumors. Throughout the studies we will closely monitor the well-being of the mice. Upon appearance of significant discomfort, animals will be sacrificed. In total 160 mice will be used. Considering extensive in vitro and in vivo experimentation in the past, we aim to use the least animals possible. Moreover, if scientific merit is not compromised, we will reduce animal group sizes throughout the project.