(6gj) Reprogramming Tumor-Clearing Macrophages with Nanotherapeutics

Macrophages (Mφs) are key immune effectors that infiltrate into the tumor in high numbers. They undergo a switch from an activated (M1) tumoricidal state to an immunosuppressive (M2) phenotype within the immunosuppressive tumor milieu, which facilitates tumor growth and metastasis. The design and manipulation of nanoparticle platforms for drug delivery is an increasingly prominent area of interest for cancer treatment; however, while many drug delivery platforms focusing on targeting macrophages have shown efficacious pre-clinical results in certain cancer types, this has not translated to a significant number of FDA approved, clinically applied nanoparticle systems. This is especially true for solid tumors such as glioblastoma, of which immune suppressive cells such as macrophages prevented effector T cells from penetrating into the solid tumor. Therefore, there is great opportunity to bring macrophage-targeting nanotherapeutics for the treatment of glioblastomas, with results that can be translated to other solid tumors. My research goals focus on using nanoparticle as biophysical probes to study the behaviors of macrophage within the tumor. This knowledge will then be used to better design and implement therapeutic nanoparticle platforms in clinically relevant models of solid tumors. My laboratory will be built on multidisciplinary work that involves a team of experts in engineering, nanomedicine, materials science, and cancer immunology. It will provide training for engineering students, cancer immunology students, and clinical fellows.

I am uniquely suited to establish a laboratory that integrates training in engineering nanoparticle platforms with an understanding of nanoparticle formulation, pharmacokinetics, and cancer-immunology. During my doctoral work with Dr. Kannan Rangaramanujam, I developed dendrimer-based targeted therapy for brain tumor and CNS inflammation. a now patented technology. These works built the guiding principles for designing nanomedicine that can efficiently target CNS diseases. Throughout my graduate studies, I led collaborations with faculty and students in the departments of neuroscience, neurology, and oncology. My postdoctoral training with Dr. Matthias Stephan and Dr. Eric Holland has built my foundation in cancer immunology, leading to experience in understanding the role of macrophages in cancer development, as well as the development of clinically relevant animal models of cancers. Based on my combined doctoral and postdoctoral work, I was recently awarded the American Brain Tumor Association Basic Research Fellowship Award.

Teaching Interests: My laboratory will provide training for engineering students, cancer immunology students, and clinical fellows.

Education

Ph.D., 2016, Johns Hopkins University, Materials Sciences and Engineering

Selected Publications

• Zhang F, Stephan SB, Ene CI, Smith TT, Holland E, Stephan MT. Nanoparticles that reshape the tumor milieu create a therapeutic window for effective T cell therapy in solid malignancies. Cancer research. 2018. canres. 0306.2018
• Zhang F*, Mastorakos P*, Mishra M, Mangraviti A, Hwang L, Zhou J, Hanes J, Brem H, Olivi A, Tyler B, Kannan RM. PAMAM Dendrimer Biodistribution in Glioblastoma and Intrinsic Targeting of Tumor Associated Macrophages. Biomaterials. 2015. 52:507-16.
• Zhang F, Magruder T, Lin YA, Crawford TC, Grimm J, Sciortino C, Wilson MA, Blue M, Kannan S, Johnston M, Baumgartner W, Kannan RM. Generation-6 hydroxyl PAMAM dendrimers for improved delivery of therapeutics to the brain in a large animal brain injury model. J Control Release. 2017. 249:173-182.
• Zhang F, Nance E, Jasty V, Mishra MK, Kambhampati SP, Zhang Z, Kannan RM, Kannan S. Surface functionality affects the biodistribution and targeting to neuroinflammation for intra-amniotically delivered dendrimers. J Control Release. 2016. 10;237:61-70.