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IRG 1 Intellectual Focus:

This interdisciplinary research group brings together a broad range of expertise in nanomaterials synthesis, modification, and characterization to address the challenges of developing applications of nanotechnology in biosensing, bioimaging, and treatment of challenging diseases such as cancer. Common scientific and technical challenges as well as a common application focus on cancer will drive interations and collaborations between participants.

 Nanoparticles as Tools

IFN Faculty Participants:

F. Aliev1, D. Banerjee2, V. Bansal3, F. Carrero4, Z. Chen1, U. Cordova4, E. Fasoli5, C. Gonzalez1, K. Griebenow1, M. Guinel1, M. Latorre4, O. Perales-Perez4, R. Raptis1, J.M. Rivera1, F. Roman4, E. Rosa-Molinar1, M. Torres-Lugo4
(University of Puerto Rico, Cayey3, Humacao5, Mayagüez4, Medical Sciences2, and Rio Piedras1)

 

IFN Strategic Partner Collaborators:

V. Rotello, University of Massachusetts, Amherst; G. Lopez-Berestein, J. Klostergaard, C. Li, A.K. Sood, MD Anderson Cancer Center; S. Sridhar, Northeastern University; J.O. Trent, James Graham Brown Cancer Center); R. Dluhy, (University of Georgia), Athens; Z. Arslan (Jackson State University, Jackson); Edmond Magner (Univeristy of Limerick, Ireland); C. Rinaldi, University of Florida, Gainesville.

 

Year 3 IRG Planning and Implementation Activities:

During the fall 2012, Torres-Lugo took the leadership of the IRG1.  For that purpose several individual meetings with IRG1 members were conducted.  These included discussion regarding future plans as a group and evolution of the IRG on the upcoming renewal.  A mentoring meeting with start up recipients was also conducted.

 

Test bed facilities were remodeled and purchased instrumentation was installed (see progress report on test bed facility).  The facility is mostly operational.  A clean room facility to isolate the cell culture area is still pending purchasing and installation due to suspension.  Work related to in vitro testing using mammalian cell cultures is limited to the current available area.

 

Year 1 Research Accomplishments for the IRG:

Bansal and Fasoli collaborated insynthesis of epoxy functionalized magnetic nanoparticles and their subsequent chemical modification to develop affinity nanosorbents for isolation of serine proteases.  Córdova constructed a Brownian dynamics simulation in order to study colloidal stability of particles synthetized by the group. Griebenow and his research group developed a smart delivery system for proteins from mesoporous silica nanoparticles. These systems deliver proteins from redox-sensitive bonds to the cytoplasm of target cells. We recently succeeded delivering Cyt c to target cells and induce apoptosis in HeLa cancer cells. We further demonstrated that our glycosylated Cyt c neoconjugates were more efficient in inducing apoptosis. Based on these exciting results we are currently developing an RO1 application. Griebenow and Cabrera developed several nanostructured enzyme-based sensors. Several constructs were improved by chemically modifying the enzymes with poly(ethylene glycol) or lactose. This resulted in prolonged lifetime of the sensors. Latorre-Esteves and Rinaldi assessed the effects of nanoparticle surface properties on nanoparticle/cell interactions. Raptis and Klostergaard imaged in vivo for the first time a human breast cancer xenograft on a nude mouse using an iron-based MRI contrast agent developed in the UPR laboratory.  Latorre-Esteves developed and studied stability and toxicity of polymeric nanocarriers designed to release therapeutic enzymes in diseased lysosomes. Latorre-Esteves and Torres-Lugo, examined effect of nanoparticle surface charge on nanoparticle plasma half-life in vivo. Torres-Lugo, Guinel, and Orange collaborated in the imaging of the cellular trafficking of magnetic nanoparticles in vivo and in vitroTorres-Lugo and Raptis performed a preliminary assessment of the stability of iron oxide contrast agents to determine in vitro cytotoxicity. Torres-Lugo and Rinaldi continued the investigation of the mechanisms underlying potentiation of chemotherapeutic agents using magnetic nanoparticles and alternating magnetic fields. Torres-Lugo investigated the effect of nanoparticle’s surface properties on in vivo biodistribution in subcutaneous and orthotopic ovarian and breast cancer models.  Recent studies included the determination of long-term in vivo toxicity of iron oxide nanoparticles as well as magnetic fluid hyperthermia experiments in vivo. These experiments were performed in collaboration with MDACC and the PRCCC. Results were very promising and are currently preparing a collaborative R01. Perales and Roman’s group have synthesized Zn-based (capped with thioglycolic acid or 3-mercaptopropionic acid) and Cd-based quantum dots (capped with thioglycolic acid or L-glutathione), and used to investigate their cytotoxicity to human pancreatic carcinoma cells (PANC-1) in absence and presence of UV-irradiation. Bailon and Perales have developed a microwave-assisted synthesis of water-soluble and photo-stable Cu-doped Zn-based QDs directly in aqueous phase with the support of 3-mercaptopropionic acid (MPA). The toxicity of light-activated QDs was evaluated in cancer cells (i.e. Human Pancreatic carcinoma cells or PANC-1) and enhanced toxicity was observed. As-synthesized Cu-doped Zn-based QDs can be considered potential candidates for nanobio-applications. Perales and Collantes produced size-controlled pure and (Fe3+ and Fe2+)-doped ZnO nanoparticles (NPs) in a polyol medium. XRD measurements confirmed the formation of well-crystallized wurtzite ZnO with absence of secondary phases in bare and doped samples.

Year 3 Collaborations with IFN Partners:

Torres-Lugo has collaborated with Rinaldi, Li, Lopez-Berenstein, and Sood to assess in vivo biodistribution and efficacy of magnetic nanoparticles developed by Rinaldi that resist aggregation in biological media. The student Karem Court (an IFN supported stuent) will be spending the 2013 summer at MDACC performing formal experiments.

 

Year 4 Work Plan for the IRG:

A working plan is pending the termination of the suspended status.