Grants and Contributions:

Grant or Award spanning more than one fiscal year (2017-2018 to 2018-2019).

The regulation of polyamine levels in cells is highly regulated and dependent upon both the synthesis andx000D
catabolism processes at work within the cell. As enzymes involved in both the synthesis (ornithinex000D
decarboxylase) and catabolism (spermine/spermidine actyl transferase 1; SSAT1) of polyamines are known tox000D
be altered under pathological conditions such as cancer, modulation of enzyme expression/activity has beenx000D
identified as a potential therapeutic target for cancer. However, fundamental obstacles impede advancementsx000D
in this area. As polyamine concentrations within the cell drive many important biological functions, a keyx000D
limitation to scientific advancement of this field has been the inability to SELECTIVELY alter the expressionx000D
of key enzymes in polyamine metabolism within DISCRETE cellular populations. A potential solution to thisx000D
problem is the use of nanoparticle systems to delivery the desired compounds to selected cell types. Byx000D
optimizing lipid and polymer based coatings and attaching targeting vectors to the surface of the nanoparticle itx000D
is possible to "tune" the nanoparticle to interact with selected cells while minimizing interactions withx000D
off-target cells. The objective of this research application is to design, characterize and provide initialx000D
proof-of-concept for targeted alteration of SSAT1 expression within a selected cell population. By optimizingx000D
the nanoparticle surface through lipid and polymer composition, as well as through the attachment of cellx000D
targeting vectors, it is hypothesized that a more effective and cell selective approach to modulation of enzymex000D
expression can be achieved. Rationale for this particular enzyme and cell is based on the over-expression ofx000D
SSAT1 observed in brain tumors and recent studies suggesting alterations in SSAT1 expression in GB couldx000D
influence cell survival. The focus of this project is to identify survival advantages of SSAT1 in GB cells andx000D
develop a cellular "tuned" nanoparticle based delivery system tailored to modulate SSAT1 expression.x000D
Ultimately the goal is to optimize nanoparticle delivery to select tumor cells while avoiding delivery to normalx000D
cell populations.