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Bioengineering Seminar Series: Anu Puri
Friday, April 1, 2011
11:00 a.m.
Room 1200, Jeong H. Kim Engineering Building
For More Information:
Professor Sameer Shah
sameer@umd.edu

Assembly and Reactivity of a Photoactivable Phospholipid in Lipid Bilayers: A Model System for on-Demand Drug Delivery Platform

Anu Puri
Membrane Structure and Function Section
Nanobiology Program
Center for Cancer Research, NCI
National Cancer Institute

We are developing lipid-based drug delivery tools using a photoactivable lipid (DC8,9PC). DC8,9PC (1,2-bis-(tricosa-10,12-diynoyl)-sn-glycero-3-phosphocholine) is a photopolymerizable lipid that exhibits unique bilayer assembly characteristics. This lipid undergoes UV (254 nm)-triggered polymerization and assumes chromogenic properties upon photo-crosslinking. To understand the effect of material properties of matrix (non-photoreactive) lipids vital for DC8,9PC polymerization, we developed liposomes from DC8,9PC and either gel (DPPC) or fluid phase (POPC) matrix lipids. For drug delivery applications, our formulations contain fluorescent marker, calcein or an anticancer agent Doxorubcin (DOX) along with a pegylated lipid (DSPE-PEG2000) for in vivo stability.

We demonstrate that UV-mediated polymerization depends on packing properties of DC8,9PC in the lipid bilayer and is favored by the gel phase but not fluid phase matrix lipids. Using various biochemical and biophysical techniques, we have analyzed the correlates of lipid packing on the degree of photoactivation of DC8,9PC and release rates of entrapped calcein. We show that calcein release is preceded by polymerization. Polymerization results in fiber-like structures in the UV-treated DPPC:DC8,9PC liposomes (cryo-electron microscopy). Molecular Dynamics (MD) simulations of DPPC:DC8,9PC bilayer indicate that lipid tails in the gel phase are more highly ordered (thus packed in close proximity to each other) than in the fluid phase POPC:DC8,9PC bilayer. We speculate that well-packed fatty acyl chains favor the probability of light-induced polymerization in DC8,9PC. Hence segregation of DC8,9PC in the lipid bilayer is essential for light-triggered release of entrapped contents. These studies may have implications in understanding the physicochemical associations (at the nanoscale) that occur in biological membranes as a result of processes such as signaling, transport, and fusion.

For biological applications (localized drug delivery), we have used a visible light source (514 nm laser) that does not affect cell viability. Exposure of DPPC:DC8,9PC liposomes to 514 nm resulted in release of entrapped calcein or DOX; however, without evidence of photopolymerization. Therefore mechanisms of UV- or visible light-triggered drug release are distinct from each other. We also demonstrate that pre-exposure of liposome/MCF-7 cell suspensions to 514 nm laser results in improved efficiency of doxorubicin delivery to cells (based on cytotoxicity assays). Our animal studies using the human nasopharyngeal carcinoma (KB)-Xenograft mouse model show that DPPC: DC8,9PC liposomes show similar biodistribution when compared with control (DC8,9PC minus) liposomes. Our formulations have the potential for light-triggered drug delivery in patients.

This Event is For: Graduate • Faculty • Post-Docs

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