April 26th CTE Seminar

Title: Engineering a Bacteria-Based Autonomous Drug Delivery System for Cancer Therapy

Presenter: Dr. Bahareh Behkam, Associate Professor, Department of Mechanical Engineering

Research group: MicroN BASE Lab

The success of chemotherapy depends not only on the efficacy of the therapeutics but also on the transport of the therapeutics to all malignant cells in sufficient concentrations. Despite significant recent progress in nanomedicine, drug delivery to solid tumors remains a formidable challenge often associated with systemic toxicity and limited extravascular transport of nanotherapeutics to cells distal from functioning blood vessels. Overcoming the aforementioned transport barriers would significantly improve the efficacy of nanomedicine for cancer therapy. Attenuated strains of tumor-targeting facultative anaerobe Salmonella enterica serovar Typhimurium have been demonstrated to have exceptionally high selectivity to primary tumors and metastatic cancer, good safety profile, and effective tumor penetration mechanisms, although in clinical trials conducted to date, complete tumor regression through bacteria monotherapy has not been achieved. We hypothesized that bacteria can be exploited to deliver nanotherapeutics to poorly vascularized and hypoxic tumor tissue, currently inaccessible to passively diffusing nanotherapeutics. To test our hypothesis, we pioneered the Nanoscale Bacteria-Enabled Drug Delivery System (NanoBEADS) in which the functional capabilities of engineered tumor-targeting Salmonella Typhimurium VNP20009 are interfaced with chemotherapeutic-loaded nanoparticles. In this talk, I will first discuss our work in biomanufacturing of NanoBEADS. I will then describe our investigation of intra-/intercellular transport of NanoBEADS in various 3D tumor spheroid in vitro models and an in vivo mammary breast cancer model. I will show that bacteria can be exploited to overcome the barriers to extravascular transport and enhance nanoparticles distribution in solid tumors by a remarkable 100-fold. Lastly, I will describe our work in combining synthetic biology and micro-bio robotics to develop a distributed network of NanoBEADS that function as an intelligent and reconfigurable swarm for controlled and targeted drug delivery. Success in the development of a distributed network of bio-hybrid microrobotic systems with programmable emergent behavior for controlled drug release could unlock a powerful new paradigm in cancer treatment towards addressing the grand challenge of solid tumor drug delivery.