| Many versatile building blocks have been designed and synthesized for the development of a platform approach towards drug delivery. These building blocks can be utilized individually or in conjunction with one another to form novel drug delivery systems. One of these building blocks is a novel dendritic molecular transporter that can be designed to localize in the cytosol or the nucleus of a cell, based upon the unique structure of each dendrimer. The cytosolic localizing transporter (MT) has been utilized to successfully deliver antibodies into virally infected cells, effectively reducing viral replication by 80–90%.;Additionally, the novel transporters have been utilized to develop a dendritic bow-tie molecule that has both molecular transporting function and multi-therapeutic carrying moieties on the periphery of the structure. This provides a novel approach for using dendrimers for both cell-penetrating and multidrug delivering purposes while increasing the therapeutic payload per delivery event as compared to the MT.;To further increase the cargo loading of a delivery system, a multifunctional nanoparticle scaffold has been developed that incorporates not only high amounts of therapeutic, but also the molecular transporter onto the vector. The nanoparticle scaffold is formed from the intramolecular cross-linking of a well-defined linear polymer utilizing an incorporated novel benzosulfone cross-linker. The covalently cross-linked nanoparticle can be modified with a variety of functionalities in a top-down approach that can be tailored for a specific application. The molecular transporter has been attached to the nanoparticle (MT-NP) and this vector as well as the cytosolic transporter has been used for the delivery of small therapeutics, such as peptides and oligonucleotides. Specifically, oligonucleotide delivery studies utilizing both MT and MT-NP showed a significant knockdown of the targeted protein lamin A/C.;Additionally, the modification of nanoparticles in a bottom-up approach has been explored through the development and utilization of a novel low temperature cross-linker that allows the intramolecular chain collapse of the linear polymer to occur at a lower temperature. The lowered temperature facilitates incorporation of functionalities into linear polymers which upon collapse yields functionalized nanoparticles. |
