(12m) Interfacing Cells and Materials for Advanced Delivery Systems

Research Interests:

The clinical translation of novel therapies and delivery systems is limited by their poor biological performance. Material-based delivery systems (e.g. nanoparticles) perform complex delivery functions such as on-demand or controlled release, but they are limited in performing basic biological functions (e.g. circulating, targeting tissues, penetrating barriers, and entering diseased cells). Cell-based therapies routinely perform these basic biological functions as they have evolved to interact with living systems, but they are not suitable for drug loading and controlled release. My research has led to the development of a number of hybrid delivery systems capable of performing both biological and synthetic functions [1-4]. These advanced delivery systems incorporate findings from my phenomenological studies [5-6], which have elucidated the key biophysical, biochemical, and material parameters that facilitate enhanced delivery.

Ph.D. Research:

My graduate research with Professor Samir Mitragotri at the University of California, Santa Barbara focused on improving the biological performance of nanoparticle delivery systems. During my Ph.D I developed three distinct blood-cell inspired hybrid systems that enhanced the in vivo delivery abilities of nanoparticles by utilizing and mimicking circulatory blood cells, including: (i) red blood cells [2-3], (ii) white blood cells [1], and (iii) platelets [4]. The first two examples utilize a strategy known as "cellular hitchhiking", which involves the attachment of polymeric particles to the surface of circulatory cells so as to transfer innate circulatory (e.g. long circulation of red blood cells) and targeting abilities (e.g. inflammation targeting of white blood cells) from cell to particle. The second strategy involves the design and application of synthetic platelets which incorporate the essential biophysical (elasticity [5] and shape [6]) and biochemical (surface biology) parameters of natural platelets into a single nanoparticle capable of performing hemostasis and preventing blood loss. During my Ph.D. I was an NSF GRFP Fellow and authored more than 25 peer-reviewed research publications in the field of drug delivery.

Postdoctoral Research:

My postdoctoral research with Professor Robert Langer at the Massachusetts Institute of Technology focuses on the development of oral drug delivery systems. I am currently expanding the broad theme of interfacing cells and materials [7] for the improved delivery of live-probiotics to the microbiome. Using a layer-by-layer encapsulation approach, I have shown that encapsulated probiotics exhibit enhanced: (i) protection against harsh gastrointestinal tract conditions, (ii) mucoadhesion and growth on intestines, and (iii) integration with the hostâ??s microbiome in vivo as compared to non-encapsulated probiotics [8]. Another focus during my postdoctoral work has been on the clinical translation of controlled release polymeric delivery systems. I am currently working with clinicians in an ongoing clinical trial investigating the bioavailability of micronutrients delivered via a novel particle-based oral delivery system.

Future Research:

As a faculty member I will focus on two research areas:

Targeted nanoparticle delivery:

(a) Biologically-active nanoparticles for enhanced tissue targeting and penetration

(b) Determining organ-level and cell-specific distribution of nanoparticles

Microbiome delivery:

(a) Microbiome modulation via delivery of encapsulated probiotics and microbes

(b) Delivery strategies to maintain a healthy microbiome during antibiotic treatments

Teaching Interests:

1. Anselmo, A. C.; Gilbert, J. B.; Kumar, S.; Gupta, V.; Cohen, R. E.; Rubner, M. F.; Mitragotri, S., Monocyte-Mediated Delivery of Polymeric Backpacks to Inflamed Tissues: A Generalized Strategy to Deliver Drugs to Treat Inflammation. Journal of Controlled Release 2015, 199, 29-36.
2. Anselmo, A. C.; Gupta, V.; Zern, B. J.; Pan, D.; Zakrewsky, M.; Muzykantov, V.; Mitragotri, S., Delivering Nanoparticles to Lungs While Avoiding Liver and Spleen through Adsorption on Red Blood Cells. ACS Nano 2013, 7, 11129-11137.
3. Anselmo, A. C.; Kumar, S.; Gupta, V.; Pearce, A. M.; Ragusa, A.; Muzykantov, V.; Mitragotri, S., Exploiting Shape, Cellular-Hitchhiking and Antibodies to Target Nanoparticles to Lung Endothelium: Synergy between Physical, Chemical and Biological Approaches. Biomaterials 2015, 68, 1-8.
4. Anselmo, A. C.; Modery-Pawlowski, C. L.; Menegatti, S.; Kumar, S.; Vogus, D. R.; Tian, L. L.; Chen, M.; Squires, T. M.; Sen Gupta, A.; Mitragotri, S., Platelet-Like Nanoparticles: Mimicking Shape, Flexibility, and Surface Biology of Platelets to Target Vascular Injuries. ACS Nano 2014, 8, 11243-11253.
5. Anselmo, A. C.; Zhang, M.; Kumar, S.; Vogus, D. R.; Menegatti, S.; Helgeson, M. E.; Mitragotri, S., Elasticity of Nanoparticles Influences Their Blood Circulation, Phagocytosis, Endocytosis, and Targeting. ACS Nano 2015, 9, 3169-3177.
6. *Kolhar, P.; *Anselmo, A. C.; Gupta, V.; Pant, K.; Prabhakarpandian, B.; Ruoslahti, E.; Mitragotri, S., Using Shape Effects to Target Antibody-Coated Nanoparticles to Lung and Brain Endothelium. Proceedings of the National Academy of Sciences 2013, 110, 10753-10758.
7. *Jaklenec, A.; *Anselmo, A. C.; Hong, J.; Vegas, A. J.; Kozminsky, M.; Langer, R.; Hammond, P. T.; Anderson, D. G., High Throughput Layer-by-Layer Films for Extracting Film Forming Parameters and Modulating Film Interactions with Cells. ACS Applied Materials Interfaces 2016, 8, 2255-2261.
8. Anselmo, A. C., McHugh, K.J., Webster, J., Langer, R., Jaklenec, A. Layer-by-Layer Encapsulation of Probiotics for Delivery to the Microbiome. In revision since July 2016.