TUMOR-PENETRATING NANOPARTICLES

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This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. We have synthesized a series of diblock and triblock copolymers and characterized the self-assembled structures in terms of drug loading efficiency and average particle size as measured by dynamic light scattering. For some of these materials, we have analyzed tissue penetration and drug delivery in vitro and in vivo. We propose to do a systematic evaluation of the effect of copolymer composition on the self-assembled structures in aqueous solutions as determined by cryo-EM imaging. We further plan to correlate the effect of supramolecular size and shape on (a) tissue penetration in vitro (as determined by a spheroid penetration assay), (b) drug release kinetics, (c) circulation halflife in vivo and (d) antitumor activity when materials are loaded with doxorubicin. We have the experience and capability to complete the proposed studies except for the cryo-EM imaging, which is a critical component of the proposed studies.