Mitochondrial Nanomedicine for Treating MultiDrug Resistant Triple Negative Breast Cancer
Lowering the apoptotic threshold of multidrug resistance cancer by fragmenting the mitochondrial network
Inhibiting Cell Communication to Prevent Metastasis and Reverse MultiDrug Resistance in Ovarian Cancer
Nanoparticles designed to inhibit cell communication via tunneling nanotubes and exosomes to prevent metastasis and reverse multidrug resistance in ovarian cancer.
Mitochondrial Nanomedicine for Treating Neurodegenerative Disease and Progeria
Increase the energy capacity and protein folding efficiency of cells by promoting mitochondrial network fusion and fusion with the endoplasmic reticulum with intranasal administered nanoparticles.
Alternative to onabotulinumtoxinA for the cosmetic treatment of wrinkles
Nanoparticles inhibiting exosomes (anti-SNARE peptide) and restoring membrane lipids (ceramide) for treating the appearance of wrinkles.
EGFR Targeted NP LON-PTX Treatment strategy
These EGFR targeted nanoparticles exploit the overexpression of growth factor receptors in hypoxic, multidrug resistant cancer and inhibit the Warburg Effect by delivering Lonidamine (a hexokinase 2 inhibitor). Lonidamine lowers the apoptotic threshold for paclitaxel and the drug combination reverses multidrug resistance in triple negative breast cancer.
SEM and ESCA of Nanoparticles
SEM and ESCA of Non-targeted and EGFR-targeted Polymeric Nanoparticles. The design of the targeting construct is also shown in Panel C. ESCA analysis confirms targeting residue on surface of nanoparticles.
Biodistribution of Targeted Nanoparticles
EGFR-targeted nanoparticles accumulate at the site of the tumor and have a similar biodistribution to non-targeted nanoparticles, yet have improved pharmacokinetics.
Targeted Nanoparticles Reduce Tumor Size and Reverse Drug Resistance
Targeted Nanoparticles Reduce Tumor Size and Reverse Drug Resistance. Combination therapy (lonidamine and paclitaxel) with EGFR-targeted nanoparticles reduce tumor size and reduce the expression of EGFR, HIF, HXK2, P-gp, and SCF.
Improved Plasma Pharmacokinetics
Treatment with EGFR-Targeted Nanoparticles Improves Plasma Pharmacokinetics.
Improved Tumor Pharmacokinetics
Treatment with EGFR-Targeted Nanoparticles Improves Tumor Pharmacokinetics.
Exploiting Cancer Biology with Nanomedicine
Dr. Milane aims to develop molecularly targeted nanomedicines that exploit the hallmarks of cancer. The therapeutic design is to develop combination strategies that manipulate two or more survival strategies of multidrug resistant cancer in one nanomedicine formulation. For example, fragmenting the mitochondrial network while inducing the endoplasmic reticulum unfolded protein response.
Cancer as Molecular Evolution
Dr. Milane has coined cancer as "survival of the fittest at its finest". Dr. Milane understands cancer in the context of molecular evolution. A cancer cell is a cell that adapts to selection pressures with the sole mission of cellular survival. Dr. Milane drew this image to illustrate cancer exosomal biology. Cancer exosomes aid survival as they function in metastasis, autocrine growth signaling, avoiding immune clearance, and macrophage polarization.
Many diseases beyond the classical mitochondrial myopathies are directly and indirectly associated with mitochondrial dysfunction. Mitochondrial dysfunction contributes to cancer, diabetes, the aging process, and neurodegenerative disease. For example, cancer is very much a mitochondrial disease as cancer cells are cells that are resistant to apoptosis, which is mediated by mitochondria. Cancer cells also revert to aerobic glycolysis (the Warburg Effect) for energy (less reliance on oxygen and mitochondrial oxidative phosphorylation and less toxic free radical production). Dr. Milane has identified the druggable targets in mitochondria and is interested developing mitochondriotropic drug delivery systems for multiple pathologies.
Dr. Milane is continually seeking to connect with other investigators and educators and enjoys productive research and teaching collaborations.