Mark Borden
801 Mudd Bldg.
Phone: +1 212 854 6955
Fax: +1 212 854 3054
Email:
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Research Interests:
Colloid science is a fascinating
field in Chemical Engineering that involves the design, fabrication and
manipulation of tiny particles dispersed in a continuous medium. Colloids abound in nature, industry and medicine
– microbubbles, vesicles and nanoparticles are all colloids. Our group takes a fundamental look at the
processes that govern the assembly and behavior of such colloids, and we apply
our findings to generalize observable phenomena and engineer innovative
constructs. Although we focus primarily
on biomedical applications (see below), we are also keenly interested in
natural and industrial systems.
Contrast Agents for Molecular Imaging
Medical imaging has revolutionized health care by giving physicians the ability to non-invasively view anatomical features and physiological processes in the body. The ultimate goal is to image the expression of key molecules associated with disease and the response to therapy. Contrast agents are extremely important in this sense – they provide a detectable enhancement (or drop) in the signal, and their presence can be quantified and tracked over space and time. In molecular imaging, contrast agents contain specific ligands that bind to target epitopes. Often, these targeted contrast agents are colloids.
One example is the microbubble.Microbubbles are tiny (~1-μm diameter) gas spheres that are stabilized by a self-assembled shell of lipids, proteins or polymers. Microbubbles are safe for injection – they do not coalesce to form emboli, but rather dissolve leaving remnants that are easily metabolized or excreted.In ultrasound, microbubbles oscillate (and even resonate) to generate a strong echo – so strong, that even a single microbubble can be detected in vivo. Ultrasound can also be used to push microbubbles (i.e., radiation force) and destroy them in the beam focus. Our goal is to engineer the microbubble surface to exploit these phenomena in the rational design of stimulus-responsive contrast agents.
Additionally, we are investigating vesicles and nanoparticles as contrast agents for other modalities, such as CT, MRI and optical imaging.
Stimulus-Responsive Delivery Vehicles
Imaging and therapy go
hand-in-hand.The vision is to oversee
the destruction of disease-causing elements (e.g., cancer cells) and
regeneration of healthy tissue. Targeting is essential to reach the misbehaving cells and reduce toxic
side effects. Often, colloidal vehicles
are employed that are designed to accumulate at the target and deliver a
therapeutic payload. Our group focuses
on engineering the loading sequence and surface features to direct
accumulation, and we employ acoustic and electromagnetic stimuli to trigger
release. One example is ultrasound-triggered
microbubble destruction in gene therapy. Microbubbles are loaded with genes (e.g., plasmids, oligos, iRNA etc.)
and injected into the circulation.Ultrasound is employed to destroy them as they pass through the beam
focus. The destruction event has two
local effects – it releases the genes and permeabilizes the vasculature – to
enhance transfection. We are designing
new microbubble formulations with increased loading capacity and circulation
persistence.
Moreover, we are looking at
vesicles and nanoparticles for drug and gene delivery.
Selected Publications:
Borden MA, Caskey CF, Little E, Gillies RJ, Ferrara KW. (2007). “DNA and polylysine loading and multilayer construction onto lipid-coated microbubbles.” submitted.
Stieger SM, Dayton PA, Borden MA, Caskey CF, Griffey SM, Wisner ER, Ferrara KW. (2007). “Imaging of angiogenesis using cadence contrast pulse sequencing and targeted contrast agents.“submitted.
Ferrara KW, Pollard R, Borden MA. (2007)“Ultrasound microbubble contrast agents: fundamentals and applications in gene and drug delivery.”in press, Annual Reviews of Biomedical Engineering.
Borden MA, Sarantos MR, Stieger SM, Simon SI, Ferrara KW, Dayton PA. (2006). “Ultrasound radiation force modulates ligand availability on ultrasound contrast agents.” Molecular Imaging, 5(3):139-147.
Borden MA, Martinez GV, Ricker JV, Tsvetokova N, Longo ML, Gillies RJ, Dayton PA, Ferrara KW. (2006). “Lateral phase separation in lipid-coated microbubbles.” Langmuir, 22: 4291-4297.
Pu G, Borden MA, Longo ML. (2006). “Collapse and shedding transitions in binary lipid monolayers coating microbubbles.” Langmuir, 22: 2993-2999.
Lum A, Borden MA, Dayton PA, Kruse DE, Simon SI, Ferrara KW. (2006). “Ultrasound radiation force enables targeted deposition of model drug carriers loaded on microbubbles.” Journal of Controlled Release, 111: 128-134.
Borden MA, Kruse D, Caskey C, Zhao S, Dayton PA, Ferrara KW. (2005). “Influence of lipid shell physicochemical properties on ultrasound-induced microbubble destruction.” IEEE Transactions on Ultrasonics, Ferroelectrics and Frequency Control, 52: 1992-2002.
Pu G, Longo ML, Borden MA. (2005). “Effect of microstructure on molecular oxygen permeation through condensed phospholipid monolayers.” Journal of the American Chemical Society. 127: 6424-6425.
Zhao S, Borden MA, Bloch S, Kruse D, Ferrara KW, Dayton PA. (2004). “Radiation force assisted targeting facilitates ultrasonic molecular imaging.” Molecular Imaging. 13: 1-14.
Borden MA, Pu G, Runner GJ, Longo ML. (2004) “Surface phase behavior and microstructure of lipid monolayer-coated microbubbles.”Colloids and Surfaces B: Biointerfaces. 35: 209-223.
Borden MA & Longo ML. (2004) “Oxygen permeability of fully condensed lipid monolayers.”Journal of Physical Chemistry B. 108(19): 6009-6016.
Borden MA & Longo ML. (2002). “Dissolution behavior of lipid monolayer-coated, air-filled microbubbles: effect of hydrophobic chain length.” Langmuir. 18(24): 9225-9233.
Gravano SM, Borden MA, von Werne T, Doerffler EM, Salazar G, Chen A, Kisak E, Zasadzinski JA, Patten TE, Longo ML. (2002) “Poly(4-(aminomethyl)styrene)-b-polystyrene: synthesis and unilamellar vesicle formation.” Langmuir 18(5): 1938-1941.