Fluorophores have been indispensable signal mediators for optical imaging. This fluorescent contrast agent can be more effective if it is specific for the target molecule and with higher sensitivity. The surface electro-magnetic (plasmon) field on the gold nanoparticles (GNPs) can be helpful for this contrast agent to have these properties by allowing artificial quenching/enhancing fluorescence. For molecular targeting particular biomolecules, aptamers are found to be as good as monoclonal antibodies, the traditional targeting agent. Aptamers also have additional beneficial properties, such as easier and cheaper production, smaller size, little immunogenicity, etc. By combining beneficial properties of fluorophores, GNPs, and aptamers, we propose to develop a molecular beacon-like nano-entity for early and accurate detection of aggressive breast cancer, with high sensitivity and specificity;and also for concurrently monitoring the efficacy of the therapeutic regimen. The nano-fluorescent agent to be developed is a breast cancer type expressing MMP-14, which is known as a marker for the breast cancer with aggressive nature. The components of this entity include a breast cancer targeting aptamer AS1411 with two Tymidine nucleotide sequences. One end of a sequence is bound to a GNP and one end of the other sequence is conjugated to Cypate, analogue of ICG (FDA approved near infrared fluorophore). The length of the chain is to be approximately a half of the distance producing the maximum fluorescence of Cypate by a GNP. The chains are connected via the substrate of MMP-14, which is small and, therefore, places the GNP and Cypate very close, forcing complete quenching. Initially, this entity emits little fluorescence because the strong plasmon field of GNP quenches the fluorescence. When it is applied to human body with breast cancer with aggressive nature, it is delivered to the breast cancer specifically via the targeting site of the AS1411 receptor. Then, it will be exposed to the MMP-14 on/in the tumor cell wall. As the substrate gets cleaved by the MMP-14, Cypate moves away from the GNP to the distance specified by the chain length, which results in highly enhanced fluorescence emission upon excitation light application. We have named this entity AptaPET (Aptamer-nanoparticle Plasmon Energy Transfer) and It allows both cancer detection and provides the information on nature of the cancer, for our system, the aggressiveness of the cancer. By selecting a special aptamer AS1411 with therapeutic properties, this entity can also be used both for detection and treatment. In addition, with no further modification, the AptaPET can be a good contrast agent for X-ray/CT. The same concept can be used for detection, diagnosis, and prognosis of other diseases as well as of other types of cancer.

Public Health Relevance

A gold nanoparticle-, Aptamer AS1411-, and NIR fluorophore Cypate-based optical contrast agent that emits its fluorescence only in the presence of MMP-14 is proposed to develop. This product can be a highly beneficial, non-invasively tool for monitoring the efficacy of on-going breast cancer treatment, providing clinicians with the guidance for the best treatment direction.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Academic Research Enhancement Awards (AREA) (R15)
Project #
1R15CA173693-01
Application #
8434567
Study Section
Nanotechnology Study Section (NANO)
Program Officer
Farahani, Keyvan
Project Start
2013-01-09
Project End
2015-12-31
Budget Start
2013-01-09
Budget End
2015-12-31
Support Year
1
Fiscal Year
2013
Total Cost
$432,018
Indirect Cost
$132,812
Name
University of Louisville
Department
Engineering (All Types)
Type
Schools of Engineering
DUNS #
057588857
City
Louisville
State
KY
Country
United States
Zip Code
40292