Frechet's Group

The Fréchet group at Berkeley will focus on the design and synthesis of biodegradable nanoscale delivery systems based mainly on dendritic macromolecules and nanoparticles, which will be applied towards the delivery of diagnostic as well as therapeutic agents. The diagnostic methods used as part of this PEN project include Positron Emission Tomography (PET), near-infrared (NIR) optical detection and Magnetic Resonance Imaging (MRI).
Our motivation is to overcome in vivo limitations that diagnostic and therapeutic agents face. These frequently suffer from low solubility leading to poor bioavailability, short circulation half-lives, systemic toxicity, or lack of stability in harsh and metabolically active media.
Dendrimer-Polyethylene oxide hybrids allow for a highly branched and non-immunogenic polyvalent scaffold with good aqueous solubility and low rate of renal filtration, thus prolonging the blood circulation lifetime of the diagnostic and therapeutic agents they carry.
Our polymer-based nanoparticles are designed to shield an encapsulated payload that can either be retained (e.g., imaging agents) or released (e.g., therapeutic drugs, proteins, or DNA) through the action of an internal or external trigger such as pH or radiation. We develop novel building blocks that enable us to tune the degradability of the nanoparticles to the needs of the desired application. Facile surface-conjugation of targeting ligands and other factors capable of boosting circulatory half-life further enhance the utility of these particles.
We explore both active and passive targeting. Typically, passive targeting takes advantage of the EPR effect present in inflamed or diseased tissue. Active targeting allows for targeting at an earlier stage of the disease. In this effort we will target vascular and pulmonary injure using α_Vβ₃ receptor ligands.
We will, use as a foundation, our previously successful designs in the area of drug delivery and immunology. We will customize these molecular structures to meet the needs of our collaborators in the School of Medicine at the Washington University in St. Louis.

The Fréchet group occupies ten synthetic chemistry laboratories in Latimer Hall on the UC Berkeley campus and three laboratories in the Material Sciences Division of the Lawrence Berkeley National Laboratory (LBNL). Group equipment frequently used for polymer synthesis and biological chemistry in support of PEN-related work includes capability for many common characterization techniques: UV and FTIR spectrophotometry, MALDI-TOF mass spectrometry, DLS, DSC, HPLC, GC, GPC, AFM, ellipsometry, and porosimetry.

Shared facilities within the College of Chemistry and among other UC Berkeley departments and at LBNL are available for additional materials characterization methods and biological work including:

• NMR (http://www.cchem.berkeley.edu/nmr/)
• SEM (http://www.lbl.gov/msd/Internal/Facilities/MSD_SEM_XRD.html#SEM)
• TEM (http://biology.berkeley.edu/EML/)
• LC/MS
• Confocal microscopy (http://microscopy.berkeley.edu/)
• Flow-cytometery (http://biology.berkeley.edu/crl/flowcytometry.shtml)
• Cell and tissue culture